Expression of <i>c‐myc</i> protein is related to cell proliferation and expression of growth factor receptors in transitional cell bladder cancer

Lipponen, P

doi:10.1002/path.1711750208

Cited by 57 publications

(35 citation statements)

References 27 publications

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“…c-Myc has been detected previously in the cytoplasm of cell lines (Craig et al 1993) and tumor samples (Lipponen 1995;Pietilainen et al 1995;Boni et al 1998). In neurons, the detection of c-Myc in Purkinje cell cytoplasm parallels the observation that N-Myc, which is expressed in the nuclei of cerebellar Purkinje neurons during development, but localizes to Purkinje cell cytoplasm in adults (Wakamatsu et al 1993).…”

Section: Discussion Cdr2 Regulation Of the Transcription Factor C-mycsupporting

confidence: 53%

The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival

Okano¹,

Park²,

Corradi³

et al. 1999

Genes & Development

111

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Paraneoplastic cerebellar degeneration (PCD) is a disorder in which breast or ovarian tumors express an onconeural antigen termed cdr2, which normally is expressed in cerebellar Purkinje neurons. This leads to an immune response to cdr2 that is associated with tumor immunity and autoimmune cerebellar degeneration. We have found that cdr2, a cytoplasmic protein harboring a helix-leucine zipper (HLZ) motif, interacts specifically with the HLZ motif of c-Myc. Both proteins colocalize in the cytoplasm of adult cerebellar Purkinje neurons, and coimmunoprecipitate from tumor cell lines and cerebellar extracts. cdr2 down-regulates c-Myc-dependent transcription in cotransfection assays, and redistributes Myc protein in the cytoplasm. Disease antisera from six of six PCD patients specifically blocked the interaction between cdr2 and c-Myc in vitro. These data indicate that cdr2 normally sequesters c-Myc in the neuronal cytoplasm, thereby down-regulating c-Myc activity, and suggest a mechanism whereby inhibition of cdr2 function by autoantibodies in PCD may contribute to Purkinje neuronal death.

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Section: Discussion Cdr2 Regulation Of the Transcription Factor C-mycsupporting

confidence: 53%

The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival

Okano¹,

Park²,

Corradi³

et al. 1999

Genes & Development

111

View full text Add to dashboard Cite

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“…We also showed enhanced expression of c-myc at both mRNA and protein levels in androgen-treated cells. The c-MYC gene has indeed been found to correlate with the proliferation of bladder cancer cells (Lipponen 1995, Schmitz-Drager et al 1997. Androgen/AR-mediated upregulation of other Wnt targets, including cyclin-D1 (Wu et al 2010) and EGFR (Zheng et al 2011), has also been demonstrated in bladder cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Androgen activates β-catenin signaling in bladder cancer cells

Zheng

Izumi

et al. 2013

Endocrine-Related Cancer

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Androgen receptor (AR) signals have been implicated in bladder carcinogenesis and tumor progression. Activation of Wnt/b-catenin signaling has also been reported to correlate with bladder cancer progression and poor patients' outcomes. However, cross talk between AR and b-catenin pathways in bladder cancer remains uncharacterized. In radical cystectomy specimens, we immunohistochemically confirmed aberrant expression of b-catenin especially in aggressive tumors. There was a strong association between nuclear expressions of AR and b-catenin in bladder tumors (PZ0.0215). Kaplan-Meier and log-rank tests further revealed that reduced membranous b-catenin expression (PZ0.0276), nuclear b-catenin expression (PZ0.0802), and co-expression of nuclear AR and b-catenin (PZ0.0043) correlated with tumor progression after cystectomy. We then assessed the effects of androgen on b-catenin in AR-positive and AR-negative bladder cancer cell lines. A synthetic androgen R1881 increased the expression of an active form of b-catenin and its downstream target c-myc only in AR-positive lines. R1881 also enhanced the activity of b-catenin-mediated transcription, which was abolished by an AR antagonist hydroxyflutamide. Using western blotting and immunofluorescence, R1881 was found to induce nuclear translocation of b-catenin when co-localized with AR. Finally, co-immunoprecipitation revealed androgeninduced associations of AR with b-catenin or T-cell factor (TCF) in bladder cancer cells. Thus, it was likely that androgen was able to activate b-catenin signaling through the AR pathway in bladder cancer cells. Our results also suggest that activation of b-catenin signaling possibly via formation of AR/b-catenin/TCF complex contributes to the progression of bladder cancer, which may enhance the feasibility of androgen deprivation as a potential therapeutic approach.

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“…Lipponen [25] showed that 34% of patients had positive c-myc and they found that c-myc expression was associated with tumor grade but with no prognostic value. Nevertheless, c -myc proved in this study that it is actively engaged in the pathogenesis of bladder cancer due to many reasons; positive c -myc expression was found in 57% of patients, its association with tumor muscle invasion and it was significantly correlated positively with both p53 and Ki-67 proteins.…”

Section: Discussionmentioning

confidence: 99%

Investigations in the molecular events of Transitional Cell Carcinoma of the Bladder

Kadhim¹,

Abdulamir²,

Hafidh³

et al. 2008

American J. of Biochemistry and Biotechnology

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Problem Statement: Transitional Cell Carcinoma (TCC) of the bladder is a significant health problem worldwide. The molecular mechanisms of tumor development and progression are complicated but likely involve the interaction of tumor suppressor genes, oncogenes, cell cycle regulatory proteins and other factors. Hence this study tries to explore the role of p53, bcl-2, c-myc and Ki-67 in TCC of the bladder in correlation with different clinicopathological criteria which are tumor grade, muscle invasion by the tumor and disease presentation, primary or recurrent tumor. Approach: Thirty patients with TCC of the bladder were involved in the period from March 2007 -May 2008. Tumors were diagnosed by histopathology and compared with 20 control subjects. The expressions of p53, bcl-2, c-myc and Ki-67 proteins were investigated by immunohistochemistry (IHC). Results: Increased expression of p53 and bcl-2 was associated with tumor grade and muscle invasion (p<0.05), but not with disease presentation (p>0.05). C -myc expression was only associated with muscle invasion (p<0.05). Ki-67 was associated with tumor grade, muscle invasion and tumor presentation (p<0.05). The correlation among these cell cycle proteins was generally significantly positive except for the correlation between bcl-2 and c-myc was poor. Conclusions: There was a significant oncogenic role of p53 and bcl-2 on TCC in terms of muscle invasion and tumor grade. C-myc was associated only with tumor invasiveness and Ki-67 proved to act as a reliable prognostic factor of TCC. This could highlight the hot targets of TCC anti-cancer therapy and the reliable targets for disease prognosis.

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Expression of c‐myc protein is related to cell proliferation and expression of growth factor receptors in transitional cell bladder cancer

Cited by 57 publications

References 27 publications

The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival

The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival

Androgen activates β-catenin signaling in bladder cancer cells

Investigations in the molecular events of Transitional Cell Carcinoma of the Bladder

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