Differential protein synthesis and expression levels in normal and neoplastic human prostate cells and their regulation by type I and II interferons

Nagano, Koki; Masters, J. R. W.; Akpan, Akunna; Yang, Alice; Corless, Steve; Wood, C.R.; Hastie, Claire; Zvelebil, Marketa; Cramer, Rainer; Naaby-Hansen, Søren

doi:10.1038/sj.onc.1207297

Cited by 55 publications

(46 citation statements)

References 42 publications

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“…Pathways Involved in Cytokine-induced ␤-Cell Death expression of BiP/GRP78 has a protective effect on ␤-cell death (36), and the present observations on decreased BiP expression is in agreement with our previous findings on an IFN-␥-induced decrease in BiP mRNA expression (37,38). Furthermore phosphorylation of BiP results in a lower binding capacity for proteins (39,40) that, together with the above described decrease in expression of non-phosphorylated BiP, may aggravate ER stress by interfering with the clearance of unfolded or misfolded proteins (41).…”

Section: Pathways Involved In Cytokine-induced ␤-Cell Deathsupporting

confidence: 83%

Proteomics Analysis of Cytokine-induced Dysfunction and Death in Insulin-producing INS-1E Cells

D’Hertog

Overbergh

Lage

et al. 2007

Molecular & Cellular Proteomics

107

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Section: Pathways Involved In Cytokine-induced ␤-Cell Deathsupporting

confidence: 83%

Proteomics Analysis of Cytokine-induced Dysfunction and Death in Insulin-producing INS-1E Cells

D’Hertog

Overbergh

Lage

et al. 2007

Molecular & Cellular Proteomics

107

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“…Enhanced expression of this hnRNP is not restricted to CML-BC, as HNRPK overexpression has also been associated with tumor progression and resistance to therapeutic drug-induced apoptosis in different types of cancer. [34][35][36][37] By assessing the mechanism whereby BCR/ABL augments HNRPK levels, we found that Hnrpk mRNA expression depends on the BCR/ABL-regulated activity of MAPK ERK1/2 . In fact, BCR/ABL-graded expression activates MAPK ERK1/2 and increases HNRPK levels in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…To assess whether the BCR/ABL-induced up-regulation of Myc expression reflects an HNRPK-dependent increase in Myc synthesis, we pulse labeled IL-3-cultured 32Dcl3 cells, and untreated and imatinib-treated 32D-BCR/ABL and S284/353A-HNRPK-expressing 32D-BCR/ABL cells with 35 [S]-methionine/cysteine and determined the levels of newly translated Myc after immunoprecipitation. Newly synthesized Myc is barely detected in 32Dcl3 cells, readily detected in BCR/ABL-expressing cells, and substantially inhibited in imatinib-treated or S284/353A-HNRPK-expressing 32D-BCR/ABL cells ( Figure 7C).…”

Section: Bcr/abl-induced Myc Expression Is Translationally Regulated mentioning

confidence: 99%

A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translation

Notari

Neviani

Santhanam

et al. 2006

Blood

176

185

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Altered mRNA translation is one of the effects exerted by the BCR/ABL oncoprotein in the blast crisis phase of chronic myelogenous leukemia (CML). Here, we report that in BCR/ABL+ cell lines and in patient-derived CML blast crisis mononuclear and CD34+ cells, p210BCR/ABL increases expression and activity of the transcriptional-inducer and translational-regulator heterogeneous nuclear ribonucleoprotein K (hnRNP K or HNRPK) in a dose- and kinase-dependent manner through the activation of the MAPKERK1/2 pathway. Furthermore, HNRPK down-regulation and interference with HNRPK translation-but not transcription-regulatory activity impairs cytokine-independent proliferation, clonogenic potential, and in vivo leukemogenic activity of BCR/ABL-expressing myeloid 32Dcl3 and/or primary CD34+ CML-BC patient cells. Mechanistically, we demonstrate that decreased internal ribosome entry site (IRES)-dependent Myc mRNA translation accounts for the phenotypic changes induced by inhibition of the BCR/ABL-ERK-dependent HNRPK translation-regulatory function. Accordingly, MYC protein but not mRNA levels are increased in the CD34+ fraction of patients with CML in accelerated and blastic phase but not in chronic phase CML patients and in the CD34+ fraction of marrow cells from healthy donors. Thus, BCR/ABL-dependent enhancement of HNRPK translation-regulation is important for BCR/ABL leukemogenesis and, perhaps, it might contribute to blast crisis transformation. (Blood. 2006;107:2507-2516)

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“…Interestingly, in the latter three both aberrant hnRNP K localisation and a correlation between protein expression and patient's prognosis were also observed. Until now, very little is known about the behaviour of hnRNP K in PCa; Nagano et al (2004) demonstrated that the hnRNP K was strongly overexpressed in PCa with respect to normal cell lines derived from the same patient and that the protein was differentially modulated in two cell lines by INF. More recently, Wang et al (2008) have shown that a novel transcriptional repressor complex containing Pura and hnRNP K binds the androgen receptor (AR) gene both in cell lines and in human prostate tissues.…”

mentioning

confidence: 99%

Heterogeneous nuclear ribonucleoprotein K: altered pattern of expression associated with diagnosis and prognosis of prostate cancer

et al. 2009

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Using proteomic analysis of the nuclear matrix (NM), we found that heterogeneous nuclear ribonucleoprotein K (hnRNP K), a member of the hnRNP family with pleiotropic functions, was differentially expressed in prostate cancer (PCa) tissues. This study aimed to characterise the expression of hnRNP K and its subcellular localisation in PCa, utilising immunohistochemical and quantitative western blot techniques. Furthermore, the hnRNP K expression was studied in human PCa cell lines in order to determine its modulation by bicalutamide, the anti-androgen widely used in PCa therapy. Immunohistochemical staining of paraffinembedded tissues showed that hnRNP K was overexpressed in PCa, where it was localised both in the cytoplasm and in the nucleus. Staining of non-tumour tissues showed exclusively nuclear localisation and a less intense or absent signal. Immunoblot analysis demonstrated that the hnRNP K level within the NM was higher in PCa compared with non-tumour tissues and closely correlated with Gleason score (P ¼ 0.008). Higher expression within the NM was significantly (P ¼ 0.032) associated with poor prognosis. In two-dimensional western blot analysis hnRNP K presented several isoforms; the one with pI 5.1 was the most differently expressed between non-tumour and PCa tissues. Preliminary results indicate that hnRNP K can be modulated in vitro by a non-steroidal antiandrogen. Taken together, our findings suggest that hnRNP K has potential implications at the diagnostic, prognostic and therapeutic levels in PCa.

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Differential protein synthesis and expression levels in normal and neoplastic human prostate cells and their regulation by type I and II interferons

Cited by 55 publications

References 42 publications

Proteomics Analysis of Cytokine-induced Dysfunction and Death in Insulin-producing INS-1E Cells

Proteomics Analysis of Cytokine-induced Dysfunction and Death in Insulin-producing INS-1E Cells

A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translation

Heterogeneous nuclear ribonucleoprotein K: altered pattern of expression associated with diagnosis and prognosis of prostate cancer

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