Objective To explore the correlation between Y-box binding protein-1 (YB-1) and P-glycoprotein (P-gp) in drug-resistant hepatocellular carcinoma (HCC) Bel-7402/ADM cells, and speculate the related mechanism of drug resistance. Methods Bel-7402/ADM cells were developed by concentration gradient escalation and intermittent administration of large dose. The levels of YB-1 mRNA and MDR1 mRNA were detected by means of RT-PCR.Western blotting was used to detect the protein expression of YB-1 and P-gp in the Bel-7402 cells and doxorubicin resistant Bel-7402 (Bel-7402/ADM) cells. Bel-7402/ADM cells were transfected with small interfering RNA (siRNA) targeting human YB-1. Expression levels of YB-1 and MDR1 mRNA and protein were detected by means of RT-PCR and Western blotting. Results IC50 values of ADM on hepatoma carcinoma cells Bel-7402 and Bel-7402/ADM were (2.23±0.07) and (7.02±0.03) μmol·L-1. The mRNA expression levels of MDR1 and YB-1 were all significantly higher in Bel-7402/ADM cells than in Bel-7402 (P<0.01). The mRNA expression levels of MDR1 and YB-1 in Bel-7402/ADM cells transfected with YB-1 siRNA were reduced significantly (P<0.01). The protein levels of YB-1 and MDR1 in Bel-7402/ADM cells transfected with YB-1 siRNA were reduced significantly (P<0.05). Conclusion These results suggest that the high expression level of YB-1 is probably correlated with multidrug resistance in HCC Bel-7402/ADM cells.
二氧化碳(CO2)培养箱(Thermo Scientific Forma Series ⅡWater-Jacketed CO2 Incubators,HEPA filter,USA);BCM-100生物洁净工作台(苏州安泰空气技术有限公司);离心机(BR4i multifunction centrifuge,Berkman,USA);冰箱(海尔公司);MLS-3780高压灭菌锅(日本三洋公司);Sunrise Remote F039300型酶联免疫仪器(澳大利亚TECAN公司);DYY-7型转移电泳仪(北京市六一仪器厂);Mx3000P实时定量荧光PCR仪(Stratagene 公司);FD201型稳压电泳仪(上海医用分析仪器厂);凝胶成像分析系统(美国Bio-Rad公司)。
MARTINF.Mechanisms of cancer:mutidrug resistance[J].,2004,1(2):229-234.
Multidrug resistance of cancer cells is a major cause for the failure of anti-cancer chemotherapy in the treatment of cancer patients; indeed, multidrug resistance usually increases during chemotherapy. It has been recognized that multidrug resistance is multifactorial and that various cellular pathways are simultaneously involved in the clinical drug resistance of cancer patients. In this review, Filipits discusses the role of transport proteins in multidrug resistance, which act by preventing the intracellular accumulation of anti-cancer drugs by pumping drugs out of cells. In addition, these transporters might also act on subcellular compartments to sequester anti-cancer drugs away from their cellular targets.
MANTWILLK,KOHLER-VARGASN,BERNSHAUSENA,et al.A inhibition of the multidrug-resistant phenotype by targeting YB-1 with a conditionally oncolytic adenovirus:implications for combinatorial treatment regimen with chemotherapeutic agents[J].,2006,66(14):7195-7202.
Bearing in mind the limited success of available treatment modalities for the therapy of multidrug-resistant tumor cells, alternative and complementary strategies need to be developed. It is known that the transcriptional activation of genes, such as MDR1 and MRP1, which play a major role in the development of a multidrug-resistant phenotype in tumor cells, involves the Y-box protein YB-1. Thus, YB-1 is a promising target for new therapeutic approaches to defeat multidrug resistance. In addition, it has been reported previously that YB-1 is an important factor in adenoviral replication because it activates transcription from the adenoviral E2-late promoter. Here, we report that an oncolytic adenovirus, named Xvir03, expressing the viral proteins E1B55k and E4orf6, leads to nuclear translocation of YB-1 and in consequence to viral replication and cell lysis in vitro and in vivo. Moreover, we show that Xvir03 down-regulates the expression of MDR1 and MRP1, indicating that recruiting YB-1 to the adenoviral E2-late promoter for viral replication is responsible for this effect. Thus, nuclear translocation of YB-1 by Xvir03 leads to resensitization of tumor cells to cytotoxic drugs. These data reveal a link between chemotherapy and virotherapy based on the cellular transcription factor YB-1 and provide the basis for formulating a model for a novel combined therapy regimen named Mutually Synergistic Therapy.
VAIMAN AV,STROMSKAYA TP,RYBALKINA EY,et al.Intracellular localization and content of YB-1 protein in multidrug resistant tumor cells[J].,2006,71(2):146-154.
Abstract The multifunctional mammalian protein YB-1 is a member of the large DNA- and RNA-binding protein family with an evolutionarily ancient cold-shock domain. YB-1 is involved in multiple DNA- and mRNA-dependent events and regulates gene expression at various levels. It can be found both in the nucleus and the cytoplasm. Bound to DNA in the cell nucleus, YB-1 functions as a transcription factor interacting with inverted CCAAT-box (Y-box) in promoters and enhancers of multiple genes. In particular, YB-1 regulates activity of the multidrug resistance (MDR) genes MDR1 and LRP. In tumors, YB-1 has been suggested to be an early and global marker of MDR. In this study, we compared amounts of YB-1 mRNAs and intracellular localization of YB-1 protein in six pairs of drug sensitive and drug resistant sublines of diverse tumors. We have shown that neither great increase in the level of YB-1 mRNA nor substantial increase in the number of cells with nuclear localization of YB-1 are obligatory traits of drug resistant tumor cell populations. However, the cells with highest amounts of YB-1 mRNA also demonstrated increased quantities of MDR1, MRP1, BCRP, and LRP mRNAs encoding different MDR proteins. Transfection of two different populations of drug-sensitive cells with YB-1 cDNA led to increase in the amount of YB-1 mRNA. The quantities of MRP1 and LRP mRNAs increased in both populations. Introduction of YB-1 small hairpin RNA (shRNA) resulted in decreased amounts of YB-1 mRNA, as well as MRP1, LRP, and MDR1 mRNAs (in three different cell lines). Our data suggest that although YB-1 regulates several MDR genes, it could not be regarded as a global marker of already formed drug resistant tumor cell populations. It is most likely that at the first steps of MDR development YB-1 activity is necessary for propagation of resistant cell populations rather than for maintenance of drug resistance.
BARGOU RC,JURCHOTTK,WAGENERC,et al.Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression[J].,1997,3(4):447-450.
Abstract Breast cancers are either primarily resistant to chemotherapy (intrinsic resistance), or respond to chemotherapy but later recur with a multidrug-resistant phenotype because of overexpression of the multidrug transporter P-glycoprotein. The MDR1 gene encoding P-glycoprotein may be transcriptionally regulated by a Y-box transcription factor. We now report that, in multidrug-resistant MCF-7 breast cancer cells, nuclear localization of YB-1 is associated with MDR-1 gene expression. In drug-sensitive MCF-7 cells, however, YB-1 was localized to the cytoplasm. Regulated overexpression of YB-1 in drug-sensitive diploid breast epithelial cells induced MDR-1 gene expression and multidrug resistance. In 27 out of 27 untreated primary breast cancers, YB-1 protein was expressed in the cytoplasm although it was undetectable in normal breast tissue of these patients. In a subgroup of tumors (9/27), however, YB-1 was also localized to the nucleus and, in these cases, high levels of P-glycoprotein were present. These results show that in a subset of untreated primary breast cancers, nuclear localization of YB-1 protein is associated with intrinsic multidrug resistance. Our data show that YB-1 has an important role in controlling MDR1 gene transcription and this finding provides a basis for the analysis of molecular mechanisms responsible for intrinsic multidrug resistance in human breast cancer.
PISAREV AV,SKABKIN MA,THOMAS AA,et al .Positive and negative effects of the major mammalian messenger ribonucleoprotein p50 on binding of 40s ribosomal subunits to the initiation codon of beta-globin mRNA[J].,2002,277(18):15445-15451.
Abstract p50, the major core protein bound to mammalian mRNAs, has been reported to stimulate translation at low p50/mRNA ratios and inhibit translation at high p50/mRNA ratios. This study aims to address the molecular mechanisms underlying these phenomena using the in vitro assembly of 48 S preinitiation complexes from fully purified translational components in the presence or absence of p50 as analyzed by the toeprint assay. With limited concentrations of eIF2, eIF3, and eIF4F, p50 (but not pyrimidine tract-binding protein, which was taken for comparison) strongly stimulates formation of the 48 S preinitiation complexes with beta-globin mRNA. This stimulation is observed when just a few molecules of p50 are bound per molecule of the mRNA. When the amount of p50 in solution is increased over some threshold p50/mRNA ratio, a remarkable repression is observed that can still be relieved by adding more eIF2 and eIF4F. At even higher concentrations of p50, the inhibitory effect becomes irreversible. The threshold ratio depends upon the extent of secondary structure of the 5'-untranslated region linked to the beta-globin coding region. Chemical probing has confirmed that the binding of p50 to mRNA involves only the sugar-phosphate backbone of the mRNA leaving nucleotide bases free for interaction with other messenger ribonucleoprotein (mRNP) components. These data are best compatible with the functional role of p50 as a "manager" of mRNA-protein interactions in mammalian mRNPs.
DE SOUZA-PINTO NC,MASON PA,HASHIGUCHIK,et al.Novel DNA mismatch-repair activity involving YB-1 in human mitochondria[J].,2009,8(6):704-719.
Maintenance of the mitochondrial genome (mtDNA) is essential for proper cellular function. The accumulation of damage and mutations in the mtDNA leads to diseases, cancer, and aging. Mammalian mitochondria have proficient base excision repair, but the existence of other DNA repair pathways is still unclear. Deficiencies in DNA mismatch repair (MMR), which corrects base mismatches and small loops, are associated with DNA microsatellite instability, accumulation of mutations, and cancer. MMR proteins have been identified in yeast and coral mitochondria; however, MMR proteins and function have not yet been detected in human mitochondria. Here we show that human mitochondria have a robust mismatch-repair activity, which is distinct from nuclear MMR. Key nuclear MMR factors were not detected in mitochondria, and similar mismatch-binding activity was observed in mitochondrial extracts from cells lacking MSH2, suggesting distinctive pathways for nuclear and mitochondrial MMR. We identified the repair factor YB-1 as a key candidate for a mitochondrial mismatch-binding protein. This protein localizes to mitochondria in human cells, and contributes significantly to the mismatch-binding and mismatch-repair activity detected in HeLa mitochondrial extracts, which are significantly decreased when the intracellular levels of YB-1 are diminished. Moreover, YB-1 depletion in cells increases mitochondrial DNA mutagenesis. Our results show that human mitochondria contain a functional MMR repair pathway in which YB-1 participates, likely in the mismatch-binding and recognition steps.
FUJIIT,SEKIN,NAMOTO-MATSUBAYASHIR,et al.YB-1 prevents apoptosis via the mTOR/STAT3 pathway in HER-2-overexpressing breast cancer cells[J].,2009,5(2):153-156.
Evaluation of: Lee C, Dhillon J, Wang MY et al.: Targeting YB-1 in HER-2 overexpressing breast cancer cells induces apoptosis via the mTOR/STAT3 pathway and suppresses tumor growth in mice. Cancer Res. 68 (21), 8661-8666 (2008). The transcription factor Y-box binding protein (YB)-1 is highly expressed in breast cancer cells and is strongly linked with breast cancer patient prognosis. In this paper, siRNA knockdown of YB-1 was used to investigate breast cancer cell proliferation. Six breast cancer cell lines that either overexpress HER-2 or were triple negative demonstrated growth inhibition following YB-1 knockdown. In particular, YB-1 knockdown induced apoptosis in BT-474-m1 and Au565 cells. Knockdown of YB-1 also decreased phosphorylation of STAT3S727, ERK1/2T202/Y204, mTORS2448 and total mTOR expression. When STAT3 was knocked down by siSTAT3, apoptosis was induced and constitutively active phosphorylated STAT3 was found to rescue YB-1-induced apoptosis. Furthermore, YB-1 knockdown remarkably suppressed colony formation in a soft agar assay, while delayed tumor formation was observed in mice. YB-1 knockdown inhibited cell growth and it is thought to involve induction of apoptosis via the mTOR/STAT3 intracellular signaling pathway. YB-1 is a promising molecular target for HER-2-overexpressing or triple-negative breast cancer cells.
OHGAT,KOIKEK,ONOM,et al.Role of the human Y box-binding protein YB-1 in cellular sensitivity to the DNA-damaging agents cisplatin,mitomycin C,and ultraviolet light[J].,1996,56(18):4224-4228.
EL-NAGGAR AM,VEINOTTE CJ,CHENGH,et al.Translational activation of HIF1 alpha by YB-1 promotes sarcoma metastasis[J].,2015,27(5):682-697.
YB-1 binds DNA and RNA and has been shown to promote epithelial-to-mesenchymal transition and metastasis of carcinomas. El-Naggar et02al. show that YB-1 also contributes to metastasis of high-risk sarcomas by binding to HIF1A mRNA and enhancing its translation.
HAB,LEE EB,CUIJ,et al.YB-1 overexpression promo-tes a TGF-beta1-induced epithelial-mesenchymal transition via Akt activation[J].,2015,458(2):347-351.
The Y-box binding protein-1 (YB-1) is a transcription/translation regulatory protein, and the expression thereof is associated with cancer aggressiveness. In the present study, we explored the regulatory effects of YB-1 during the transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma cells. Downregulation of YB-1 increased E-cadherin promoter activity, and upregulation of YB-1 decreased promoter activity, suggesting that the YB-1 level may be correlated with the EMT. TGF-β1 induced YB-1 expression, and TGF-β1 translocated cytosolic YB-1 into the nucleus. YB-1 overexpression promoted TGF-β1-induced downregulation of epithelial markers, upregulation of mesenchymal markers, and cell migration. Moreover, YB-1 overexpression enhanced the expression of E-cadherin transcriptional repressors via TGF-β1-induced Akt activation. Our findings afford new insights into the role played by YB-1 in the TGF-β1 signaling pathway.
JUNGK,WUF,WANGP,et al.YB-1 regulates Sox2 to coordinately sustain stemness and tumorigenic properties in a phenotypically distinct subset of breast cancer cells[J].,2014,14(1):1-13.
Background Increased collagen deposition provides physical and biochemical signals to support tumor growth and invasion during breast cancer development. Therefore, inhibition of collagen synthesis and deposition has been considered a strategy to suppress breast cancer progression. Collagen prolyl-4-hydroxylase ?? subunit 2 (P4HA2), an enzyme hydroxylating proline residues in -X-Pro-Gly- sequences, is a potential therapeutic target for the disorders associated with increased collagen deposition. However, expression and function of P4HA2 in breast cancer progression are not well investigated. Methods Gene co-expression analysis was performed in the published microarray datasets to identify potential regulators of collagen I, III, and IV in human breast cancer tissue. Expression of P4HA2 was silenced by shRNAs, and its activity was inhibited by 1, 4-DPCA, a prolyl-4-hydroxylase inhibitor. Three-dimensional culture assay was used to analyze roles of P4HA2 in regulating malignant phenotypes of breast cancer cells. Reduced deposition of collagen I and IV was detected by Western blotting and immunofluorescence. Control and P4HA2-silenced breast cancer cells were injected into fat pad and tail vein of SCID mice to examine effect of P4HA2 on tumor growth and lung metastasis. Results Using gene co-expression analysis, we showed that P4HA2 was associated with expression of Col1A1, Col3A1, and Col4A1 during breast cancer development and progression. P4HA2 mRNA levels were significantly upregulated in breast cancer compared to normal mammary tissue. Increased mRNA levels of P4HA2 correlated with poor clinical outcome in breast cancer patients, which is independent of estrogen receptor status. Silencing P4HA2 expression or treatment with the P4HA inhibitor significantly inhibited cell proliferation and suppressed aggressive phenotypes of breast cancer cells in 3D culture, accompanied by reduced deposition of collagen I and IV. We also found that knockdown of P4HA2 inhibited mammary tumor growth and metastasis to lungs in xenograft models. Conclusion These results suggest the critical role of P4HA2 in breast cancer progression and identify P4HA2 as a potential therapeutic target and biomarker for breast cancer progression.
WANGX,GUO XB,SHEN XC,et al.Prognostic role of YB-1 expression in breast cancer:a meta-analysis[J].,2015,8(2):1780-1791.
In published studies, Y-box binding protein-1 (YB-1) correlated with the prognosis of patients with breast cancer (BC), but the specific role of YB-1 is still unclear. Our study aimed to evaluate the prognostic value of YB-1 in BC patients using meta-analysis based on the published studies.We searched the relevant literatures deadline for June 2014 in databases, including PubMed, Embase, Medline and Cochrane library, and finally 8 studies were included in our study. Our study contained 1094 BC patients with 398 YB-1 positive and 696 YB-1 negative.Our results showed that YB-1 abnormal expression did not correlated with the lymph node status [OR = 1.258, 95% CI = 0.895-1.769, P = 0.186], high histological grade [OR = 2.709, 95% CI = 0.861-8.530, P = 0.089], histological type [OR = 0.837, 95% CI = 0.526-1.331, P = 0.452], P53 status [OR = 2.006, 95% CI 0.686-5.865, P = 0.203] and PR [OR = 0.607, 95% CI = 0.347-1.061, P = 0.080] in BC patients. But YB-1 over-expression was associated with other unfavorable factors: ER negativity [OR = 0.604, 95% CI = 0.388-0.941, P = 0.026], HER2 positivity [OR = 3.841, 95% CI = 2.637-5.594, P = 0.000], and high tumorous T stage [OR = 2.169, 95% CI = 1.295-3.632, P = 0.003]. In addition, our data suggested that high YB-1 expression had an adverse impact on 5-year OS [RR = 2.767, 95% CI = 2.054-3.727, P = 0.000] in BC patients.Our findings implied that YB-1 might a novel biomarker to predict the prognosis of BC, and could be a potential direction for developing diagnostic and therapeutic approaches in BC.
NISHIOS,USHIJIMAK,YAMAGUCHIT,et al.Nuclear Y-box-binding protein-1 is a poor prognostic marker and related to epidermal growth factor receptor in uterine cervical cancer[J].,2014,132(3):703-708.
Y-box binding protein-1 (YB-1) is a member of the cold shock protein family and functions in transcription and translation. Many studies indicate that YB-1 is strongly expressed in tumor cells and is considered a marker of tumor aggressiveness and clinical prognosis. Overexpression of epidermal growth factor receptor (EGFR) has been associated with poor outcomes in cervical cancer. Clinical trials of EGFR family-base therapy are currently being initiated in cervical cancer. Nuclear YB-1 expression correlates with EGFR expression in various types of cancer. However, the clinical significance of nuclear YB-1 expression in different settings, the correlation with EGFR, and the prognostic implications of YB-1 expression in cervical cancer remain elusive.Nuclear YB-1 expression was immunohistochemically analyzed in tissue specimens obtained from 204 patients with cervical cancer who underwent surgery. Associations of nuclear YB-1 expression with clinicopathological factors such as survival, EGFR expression, and human epidermal growth factor receptor 2 (HER2) expression were investigated.Nuclear YB-1 expression was found in 41 (20.2%) of 204 cases of cervical cancer and correlated with disease stage, tumor diameter, stromal invasion, and lymph-node metastasis. Nuclear YB-1 expression also correlated with EGFR expression (P=0.0114) as well as HER2 expression (P=0.0053). Kaplan-Meier survival analysis showed that nuclear YB-1 expression was significantly associated with poor progression-free survival (P=0.0033) and overall survival (P=0.0003), respectively.Nuclear YB-1 expression is a prognostic marker and correlates with EGFR expression in cervical cancer.
GUO TT,YUY,YIP WC,et al.Y-box binding protein 1 is correlated with lymph node metastasis in intestinal type of gastric cancer[J].,2015,66(4):491-499.
Y-box binding protein-1 (YB-1) is known to modulate gene transcription and protein translation, as well as cellular response to drug treatment. The aim of this study is to correlate YB-1 protein expression levels with clinicopathological parameters in intestinal-type gastric cancer tissue samples (as categorized by the Lauren classification) and substantiate the findings with in vitro experimentation.Paraffin-embedded samples from 167 patients with intestinal-type gastric cancer were used for the construction of tissue microarrays (TMAs). TMA slides were immunostained and YB-1 immunoreactivity score was based on the weighted average intensity score. Univariate analysis revealed that YB-1 immunohistochemical expression was correlated significantly with lymph node status (P = 0.054, borderline significance) and perforation (P = 0.043). YB-1 expression was also found to be an independent predictor of lymph node spread by multivariate analysis. Furthermore, siRNA-mediated YB-1 gene knockdown in MKN7 gastric cancer cells (which is known to originate from an intestinal-type gastric cancer tissue) inhibited cell migration (P = 0.0002) and invasion in vitro (P = 0.0129) significantly.YB-1 expression is associated with lymph node spread in intestinal-type gastric cancer and is a potential prognostic biomarker in this subtype of gastric cancer.
... 肿瘤多药耐药(multidrug resistance,MDR)是指一种药物作用于肿瘤使之产生耐药性后,该肿瘤对未接触过、结构无关、机制各异的多种抗肿瘤药也具有交叉耐药的现象,是肿瘤耐药的主要原因.其机制与拓扑异构酶(TOPOⅡ)、P-糖蛋白(P-glycoprotein,P-gp)、谷胱甘肽S转移酶(GST-α)等的表达、凋亡相关通路改变等因素有关[1].ABC(ATP-binding cassette)超家族转运体蛋白能够将药物分子排移至胞外,减弱其对细胞的毒性,导致肿瘤细胞耐药性的产生.此类蛋白包括P-gp、MRP、BCRP/ABCG2等,其中P-gp是最重要的耐药相关蛋白,由MDR1(即ATP-binding cassette sub-family B member 1,ABCB1)基因编码.Y-box 结合蛋白是一类特异性结合目的基因启动子和增强子内部Y-box 序列(CTGATTGGCCAA)的转录因子,广泛存在于从细菌到人类的许多物种中[2-3],发挥多种重要生物学功能.Y-box结合蛋白1(Y-box binding protein-1,YB-1)是Y-box 结合蛋白家族的成员之一,现已有大量证据表明,YB-1 与肿瘤的发生和维持存在广泛密切的联系[4-5].YB-1 在肿瘤的发生中发挥多种重要作用,不仅促进癌细胞过度增殖和抗凋亡,还协助肿瘤扩散和转移,并直接参与染色体异常和癌组织耐药性的产生.诸多学者研究提示YB-1与人乳腺癌、肺癌、结直肠癌等的MDR密切相关[6-8],但YB-1的表达与人肝癌耐药细胞株Bel-7402/ADM(多柔比星)多药耐药的关系尚未检索到有关报道.笔者在本研究比较YB-1siRNA转染耐药细胞前后YB-1和MDR1在 mRNA水平和蛋白水平的变化,探讨YB-1与Bel-7402/ADM多药耐药的关系,为改善耐药状况的新型策略提供基础研究支持和参考. ...
A inhibition of the multidrug-resistant phenotype by targeting YB-1 with a conditionally oncolytic adenovirus:implications for combinatorial treatment regimen with chemotherapeutic agents
1
2006
... 肿瘤多药耐药(multidrug resistance,MDR)是指一种药物作用于肿瘤使之产生耐药性后,该肿瘤对未接触过、结构无关、机制各异的多种抗肿瘤药也具有交叉耐药的现象,是肿瘤耐药的主要原因.其机制与拓扑异构酶(TOPOⅡ)、P-糖蛋白(P-glycoprotein,P-gp)、谷胱甘肽S转移酶(GST-α)等的表达、凋亡相关通路改变等因素有关[1].ABC(ATP-binding cassette)超家族转运体蛋白能够将药物分子排移至胞外,减弱其对细胞的毒性,导致肿瘤细胞耐药性的产生.此类蛋白包括P-gp、MRP、BCRP/ABCG2等,其中P-gp是最重要的耐药相关蛋白,由MDR1(即ATP-binding cassette sub-family B member 1,ABCB1)基因编码.Y-box 结合蛋白是一类特异性结合目的基因启动子和增强子内部Y-box 序列(CTGATTGGCCAA)的转录因子,广泛存在于从细菌到人类的许多物种中[2-3],发挥多种重要生物学功能.Y-box结合蛋白1(Y-box binding protein-1,YB-1)是Y-box 结合蛋白家族的成员之一,现已有大量证据表明,YB-1 与肿瘤的发生和维持存在广泛密切的联系[4-5].YB-1 在肿瘤的发生中发挥多种重要作用,不仅促进癌细胞过度增殖和抗凋亡,还协助肿瘤扩散和转移,并直接参与染色体异常和癌组织耐药性的产生.诸多学者研究提示YB-1与人乳腺癌、肺癌、结直肠癌等的MDR密切相关[6-8],但YB-1的表达与人肝癌耐药细胞株Bel-7402/ADM(多柔比星)多药耐药的关系尚未检索到有关报道.笔者在本研究比较YB-1siRNA转染耐药细胞前后YB-1和MDR1在 mRNA水平和蛋白水平的变化,探讨YB-1与Bel-7402/ADM多药耐药的关系,为改善耐药状况的新型策略提供基础研究支持和参考. ...
Intracellular localization and content of YB-1 protein in multidrug resistant tumor cells
1
2006
... 肿瘤多药耐药(multidrug resistance,MDR)是指一种药物作用于肿瘤使之产生耐药性后,该肿瘤对未接触过、结构无关、机制各异的多种抗肿瘤药也具有交叉耐药的现象,是肿瘤耐药的主要原因.其机制与拓扑异构酶(TOPOⅡ)、P-糖蛋白(P-glycoprotein,P-gp)、谷胱甘肽S转移酶(GST-α)等的表达、凋亡相关通路改变等因素有关[1].ABC(ATP-binding cassette)超家族转运体蛋白能够将药物分子排移至胞外,减弱其对细胞的毒性,导致肿瘤细胞耐药性的产生.此类蛋白包括P-gp、MRP、BCRP/ABCG2等,其中P-gp是最重要的耐药相关蛋白,由MDR1(即ATP-binding cassette sub-family B member 1,ABCB1)基因编码.Y-box 结合蛋白是一类特异性结合目的基因启动子和增强子内部Y-box 序列(CTGATTGGCCAA)的转录因子,广泛存在于从细菌到人类的许多物种中[2-3],发挥多种重要生物学功能.Y-box结合蛋白1(Y-box binding protein-1,YB-1)是Y-box 结合蛋白家族的成员之一,现已有大量证据表明,YB-1 与肿瘤的发生和维持存在广泛密切的联系[4-5].YB-1 在肿瘤的发生中发挥多种重要作用,不仅促进癌细胞过度增殖和抗凋亡,还协助肿瘤扩散和转移,并直接参与染色体异常和癌组织耐药性的产生.诸多学者研究提示YB-1与人乳腺癌、肺癌、结直肠癌等的MDR密切相关[6-8],但YB-1的表达与人肝癌耐药细胞株Bel-7402/ADM(多柔比星)多药耐药的关系尚未检索到有关报道.笔者在本研究比较YB-1siRNA转染耐药细胞前后YB-1和MDR1在 mRNA水平和蛋白水平的变化,探讨YB-1与Bel-7402/ADM多药耐药的关系,为改善耐药状况的新型策略提供基础研究支持和参考. ...
Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression
1
1997
... 肿瘤多药耐药(multidrug resistance,MDR)是指一种药物作用于肿瘤使之产生耐药性后,该肿瘤对未接触过、结构无关、机制各异的多种抗肿瘤药也具有交叉耐药的现象,是肿瘤耐药的主要原因.其机制与拓扑异构酶(TOPOⅡ)、P-糖蛋白(P-glycoprotein,P-gp)、谷胱甘肽S转移酶(GST-α)等的表达、凋亡相关通路改变等因素有关[1].ABC(ATP-binding cassette)超家族转运体蛋白能够将药物分子排移至胞外,减弱其对细胞的毒性,导致肿瘤细胞耐药性的产生.此类蛋白包括P-gp、MRP、BCRP/ABCG2等,其中P-gp是最重要的耐药相关蛋白,由MDR1(即ATP-binding cassette sub-family B member 1,ABCB1)基因编码.Y-box 结合蛋白是一类特异性结合目的基因启动子和增强子内部Y-box 序列(CTGATTGGCCAA)的转录因子,广泛存在于从细菌到人类的许多物种中[2-3],发挥多种重要生物学功能.Y-box结合蛋白1(Y-box binding protein-1,YB-1)是Y-box 结合蛋白家族的成员之一,现已有大量证据表明,YB-1 与肿瘤的发生和维持存在广泛密切的联系[4-5].YB-1 在肿瘤的发生中发挥多种重要作用,不仅促进癌细胞过度增殖和抗凋亡,还协助肿瘤扩散和转移,并直接参与染色体异常和癌组织耐药性的产生.诸多学者研究提示YB-1与人乳腺癌、肺癌、结直肠癌等的MDR密切相关[6-8],但YB-1的表达与人肝癌耐药细胞株Bel-7402/ADM(多柔比星)多药耐药的关系尚未检索到有关报道.笔者在本研究比较YB-1siRNA转染耐药细胞前后YB-1和MDR1在 mRNA水平和蛋白水平的变化,探讨YB-1与Bel-7402/ADM多药耐药的关系,为改善耐药状况的新型策略提供基础研究支持和参考. ...
et al .Positive and negative effects of the major mammalian messenger ribonucleoprotein p50 on binding of 40s ribosomal subunits to the initiation codon of beta-globin mRNA
1
2002
... 肿瘤多药耐药(multidrug resistance,MDR)是指一种药物作用于肿瘤使之产生耐药性后,该肿瘤对未接触过、结构无关、机制各异的多种抗肿瘤药也具有交叉耐药的现象,是肿瘤耐药的主要原因.其机制与拓扑异构酶(TOPOⅡ)、P-糖蛋白(P-glycoprotein,P-gp)、谷胱甘肽S转移酶(GST-α)等的表达、凋亡相关通路改变等因素有关[1].ABC(ATP-binding cassette)超家族转运体蛋白能够将药物分子排移至胞外,减弱其对细胞的毒性,导致肿瘤细胞耐药性的产生.此类蛋白包括P-gp、MRP、BCRP/ABCG2等,其中P-gp是最重要的耐药相关蛋白,由MDR1(即ATP-binding cassette sub-family B member 1,ABCB1)基因编码.Y-box 结合蛋白是一类特异性结合目的基因启动子和增强子内部Y-box 序列(CTGATTGGCCAA)的转录因子,广泛存在于从细菌到人类的许多物种中[2-3],发挥多种重要生物学功能.Y-box结合蛋白1(Y-box binding protein-1,YB-1)是Y-box 结合蛋白家族的成员之一,现已有大量证据表明,YB-1 与肿瘤的发生和维持存在广泛密切的联系[4-5].YB-1 在肿瘤的发生中发挥多种重要作用,不仅促进癌细胞过度增殖和抗凋亡,还协助肿瘤扩散和转移,并直接参与染色体异常和癌组织耐药性的产生.诸多学者研究提示YB-1与人乳腺癌、肺癌、结直肠癌等的MDR密切相关[6-8],但YB-1的表达与人肝癌耐药细胞株Bel-7402/ADM(多柔比星)多药耐药的关系尚未检索到有关报道.笔者在本研究比较YB-1siRNA转染耐药细胞前后YB-1和MDR1在 mRNA水平和蛋白水平的变化,探讨YB-1与Bel-7402/ADM多药耐药的关系,为改善耐药状况的新型策略提供基础研究支持和参考. ...
Novel DNA mismatch-repair activity involving YB-1 in human mitochondria
2
2009
... 肿瘤多药耐药(multidrug resistance,MDR)是指一种药物作用于肿瘤使之产生耐药性后,该肿瘤对未接触过、结构无关、机制各异的多种抗肿瘤药也具有交叉耐药的现象,是肿瘤耐药的主要原因.其机制与拓扑异构酶(TOPOⅡ)、P-糖蛋白(P-glycoprotein,P-gp)、谷胱甘肽S转移酶(GST-α)等的表达、凋亡相关通路改变等因素有关[1].ABC(ATP-binding cassette)超家族转运体蛋白能够将药物分子排移至胞外,减弱其对细胞的毒性,导致肿瘤细胞耐药性的产生.此类蛋白包括P-gp、MRP、BCRP/ABCG2等,其中P-gp是最重要的耐药相关蛋白,由MDR1(即ATP-binding cassette sub-family B member 1,ABCB1)基因编码.Y-box 结合蛋白是一类特异性结合目的基因启动子和增强子内部Y-box 序列(CTGATTGGCCAA)的转录因子,广泛存在于从细菌到人类的许多物种中[2-3],发挥多种重要生物学功能.Y-box结合蛋白1(Y-box binding protein-1,YB-1)是Y-box 结合蛋白家族的成员之一,现已有大量证据表明,YB-1 与肿瘤的发生和维持存在广泛密切的联系[4-5].YB-1 在肿瘤的发生中发挥多种重要作用,不仅促进癌细胞过度增殖和抗凋亡,还协助肿瘤扩散和转移,并直接参与染色体异常和癌组织耐药性的产生.诸多学者研究提示YB-1与人乳腺癌、肺癌、结直肠癌等的MDR密切相关[6-8],但YB-1的表达与人肝癌耐药细胞株Bel-7402/ADM(多柔比星)多药耐药的关系尚未检索到有关报道.笔者在本研究比较YB-1siRNA转染耐药细胞前后YB-1和MDR1在 mRNA水平和蛋白水平的变化,探讨YB-1与Bel-7402/ADM多药耐药的关系,为改善耐药状况的新型策略提供基础研究支持和参考. ...