YB‐1 is upregulated during prostate cancer tumor progression and increases P‐glycoprotein activity

Gimenez‐Bonafé, Pepita; Fedoruk, Matthew N.; Whitmore, Tanis G.; Akbari, Majid; Ralph, Jody L.; Ettinger, Susan; Gleave, Martin; Nelson, Colleen C.

doi:10.1002/pros.20023

Cited by 150 publications

(125 citation statements)

References 39 publications

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“…Elevated levels of the transcription elongation factor TCEB1͞Elongin C are associated with advanced androgen-independent prostate cancers (20), and changes in the subcellular localization of the membrane metalloendopeptidase MME͞CD10 expression are linked to prostate cancer grade (21). Immunohistochemical analysis of the Akt-regulated transcriptional repressor NSEP͞YB-1 demonstrates a strong positive correlation with Gleason grade (22). NSEP͞YB-1 may influence cancer progression through multiple mechanisms that include enhancement of anchorage-independent cell growth and upregulation of the p-glycoprotein multidrug-resistance protein (22,23).…”

Section: Resultsmentioning

confidence: 99%

“…Immunohistochemical analysis of the Akt-regulated transcriptional repressor NSEP͞YB-1 demonstrates a strong positive correlation with Gleason grade (22). NSEP͞YB-1 may influence cancer progression through multiple mechanisms that include enhancement of anchorage-independent cell growth and upregulation of the p-glycoprotein multidrug-resistance protein (22,23).…”

Section: Resultsmentioning

confidence: 99%

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A molecular correlate to the Gleason grading system for prostate adenocarcinoma

True

Coleman²,

Hawley

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

259

225

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Adenocarcinomas of the prostate can be categorized into tumor grades based on the extent to which the cancers histologically resemble normal prostate glands. Because grades are surrogates of intrinsic tumor behavior, characterizing the molecular phenotype of grade is of potential clinical importance. To identify molecular alterations underlying prostate cancer grades, we used microdissection to obtain specific cohorts of cancer cells corresponding to the most common Gleason patterns (patterns 3, 4, and 5) from 29 radical prostatectomy samples. We paired each cancer sample with matched benign lumenal prostate epithelial cells and profiled transcript abundance levels by microarray analysis. We identified an 86-gene model capable of distinguishing low-grade (pattern 3) from high-grade (patterns 4 and 5) cancers. This model performed with 76% accuracy when applied to an independent set of 30 primary prostate carcinomas. Using tissue microarrays comprising >800 prostate samples, we confirmed a significant association between high levels of monoamine oxidase A expression and poorly differentiated cancers by immunohistochemistry. We also confirmed grade-associated levels of defender against death (DAD1) protein and HSD17␤4 transcripts by immunohistochemistry and quantitative RT-PCR, respectively. The altered expression of these genes provides functional insights into grade-associated features of therapy resistance and tissue invasion. Furthermore, in identifying a profile of 86 genes that distinguish high-from low-grade carcinomas, we have generated a set of potential targets for modulating the development and progression of the lethal prostate cancer phenotype.carcinoma ͉ monoamine oxidase A ͉ microarray ͉ expression profile

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A molecular correlate to the Gleason grading system for prostate adenocarcinoma

True

Coleman²,

Hawley

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

259

225

View full text Add to dashboard Cite

show abstract

“…Immunohistochemistry has established an association between high levels of nuclear YB-1, tumor progression and drug resistance; nuclear YB-1 is therefore regarded as a poor prognostic indicator of patient outcome (Oda et al, 1998(Oda et al, , 2003Shibahara et al, 2001;Kohno et al, 2003;Gimenez-Bonafe et al, 2004;Chatterjee et al, 2008). We sought to evaluate the proposed proteolytic mechanism of YB-1 nuclear activation, given its direct relevance to the validity of the numerous immunohistochemical studies performed with C-terminal YB-1 antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…MDR1 induction by YB-1 is manifest by the correlation between drug resistance of breast cancers and YB-1 overexpression (Bargou et al, 1997). Furthermore, immunohistochemical analysis of a variety of drug-resistant cancers and cell lines has established a relationship between nuclear YB-1, tumor drug resistance and poor patient outcome (Oda et al, 1998(Oda et al, , 2003Shibahara et al, 2001;Kohno et al, 2003;Gimenez-Bonafe et al, 2004;Chatterjee et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Genotoxic stress-induced nuclear localization of oncoprotein YB-1 in the absence of proteolytic processing

Cohen

Valova

et al. 2009

Oncogene

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Y-box-binding protein 1 (YB-1) is an oncogenic transcription factor whose overexpression and nuclear localization is associated with tumor progression and drug resistance. Transcriptional activation of YB-1 in response to genotoxic stress is believed to occur in the cytoplasm through sequence-specific endoproteolytic cleavage by the 20S Proteasome, followed by nuclear translocation of cleaved YB-1. To study the proteolysis model, we developed a two-step affinity purification of endogenous YB-1 protein species and characterized the products using mass spectrometry. Whereas full-length YB-1 was readily identified, the smaller protein band thought to be activated YB-1 was identified as hnRNP A1. An antibody specific for YB-1 was generated, which revealed only one YB-1 species, even after genotoxic stress-induced nuclear YB-1 translocation. These findings warrant re-evaluation of the mechanism of YB-1 nuclear translocation and transcriptional activation. The relationship between nuclear YB-1 and tumor progression may also have to re-evaluated in some cases.

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“…Abnormal YB-1 staining has been found in several cancer types, including breast cancer (Bargou et al, 1997), osteosarcoma (Oda et al, 1998), ovarian adenosarcoma (Kamura et al, 1999), colorectal carcinoma (Shibao et al, 1999), lung cancer (Gu et al, 2001), and prostate cancer (Gimenez-Bonafe et al, 2004). Nuclear localization of YB-1 in breast tumor samples correlated with expression of the multidrug resistance gene MDR1 (Bargou et al, 1997) and YB-1 was found to be directly involved in MDR1 gene activation in response to genotoxic stress .…”

Section: Introductionmentioning

confidence: 99%

Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells

et al. 2005

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The epidermal growth factor receptor (EGFR) is linked to poor outcome in breast cancer, and resistance to hormonal therapy is often accompanied by activation of growth factor receptors. To investigate the mechanism(s) by which EGFR becomes activated in breast cancer, we screened a cDNA expression library for genes that mediate EGF-independent proliferation of human mammary epithelial cells (HMECs). We isolated the NSEP1 cDNA encoding Y-box-binding protein 1 (YB-1), a multifunctional transcriptional and translational regulator. This cDNA conferred growth factor independence to HMECs. YB-1-transduced cells overexpressed EGFR, but ErbB-2 (Her-2/neu) levels were unchanged. Moreover, EGFR was constitutively phosphorylated in the absence of exogenous ligand. In these cells, an EGFR-blocking antibody failed to inhibit proliferation, conditioned medium activity could not be detected, and the synthesis of EGFR ligands was reduced compared to parental cells. This suggests that EGFR is activated in a ligandindependent fashion. However, cell growth could be blocked with an ErbB kinase inhibitor, indicating that EGFR signaling plays a major role in YB-1-induced growth factor independence. Taken together, our results demonstrate that YB-1 overexpression can induce EGF independence in HMECs via activation of the EGFR pathway. This could represent one of the mechanisms by which YB-1 contributes to breast tumor aggressiveness.

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YB‐1 is upregulated during prostate cancer tumor progression and increases P‐glycoprotein activity

Cited by 150 publications

References 39 publications

A molecular correlate to the Gleason grading system for prostate adenocarcinoma

A molecular correlate to the Gleason grading system for prostate adenocarcinoma

Genotoxic stress-induced nuclear localization of oncoprotein YB-1 in the absence of proteolytic processing

Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells

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