Over-expression and amplification of the c-myc gene in human urothelial carcinoma

Christoph, Frank; Schmidt, Bettina; Schmitz‐Dräger, Bernd J.; Schulz, Wolfgang A.

doi:10.1002/(sici)1097-0215(19990420)84:2<169::aid-ijc13>3.0.co;2-f

Cited by 41 publications

(34 citation statements)

References 17 publications

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“…Although numbers are too low to allow conclusions, these findings suggest that at least in some pancreatic cancers, c-MYC alterations occur in preinvasive stages of tumor development. Reports on c-MYC deregulation in premalignant lesions of the bladder and colon (23)(24)(25) are in support of our findings. In this study, activation of c-MYC (either by gene amplification or protein overexpression) was found less frequently in lymph node metastases as compared with primary pancreatic tumors, and it did not correlate with either tumor stage or tumor size.…”

Section: Discussionsupporting

confidence: 90%

“…Discrepancy between c-MYC gene amplification and protein overexpression has also been described in bladder and colon cancers. It was therefore concluded that c-MYC amplification represents only one of multiple possible mechanisms leading to enhanced protein expression in various neoplasias (20,(23)(24)(25). Overall, the functional aspects of c-MYC gene amplification and protein overexpression remain unknown.…”

Section: Discussionmentioning

confidence: 99%

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c-MYC Activation in Primary and Metastatic Ductal Adenocarcinoma of the Pancreas: Incidence, Mechanisms, and Clinical Significance

et al. 2002

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

c-MYC Activation in Primary and Metastatic Ductal Adenocarcinoma of the Pancreas: Incidence, Mechanisms, and Clinical Significance

et al. 2002

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“…Furthermore, in some cases CCND1 itself is amplified (Proctor et al, 1991). Increased expression of MYC is found in almost all TCC, and is correlated with increased gene copy numbers (Christoph et al, 1999) and/or overexpression of the EGF receptor (Lipponen, 1995). Thus, upregulation of MYC or CCND1, required for the proliferation of TCC cells, is likely achieved by mechanisms other than activation of WNT/b-catenin signalling.…”

Section: Discussionmentioning

confidence: 99%

E-cadherin involved in inactivation of WNT/β-catenin signalling in urothelial carcinoma and normal urothelial cells

et al. 2003

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Constitutive activation of WNT signalling through b-catenin, which leads to increased transcription of TCF/b-catenin target genes, is crucial in the development of many human tumour types including colorectal carcinoma and hepatoma. Its role in urothelial cancer (TCC) is unclear, since typical activating mutations are not found. We therefore determined the activity of a b-catenin/TCFdependent promoter in proliferating normal uroepithelial cells and seven TCC cell lines, using a hepatoma line with oncogenic b-catenin as a control. Neither normal urothelial cells nor TCC lines exhibited activity under normal growth conditions. In normal cells and 5/7 TCC lines, even transfection of activated b-catenin did not restore promoter activity, suggesting repression of b-catenin/ TCF activity. TCF mRNAs and total b-catenin protein levels did not differ qualitatively between inducible and noninducible cell lines, but E-cadherin expression was lacking or low in inducible TCC lines. In these, cotransfection of E-cadherin diminished activation of the TCF-dependent promoter by b-catenin. Our results make constitutive WNT/b-catenin signalling in TCC appear unlikely, thereby explaining the lack of reported mutations. However, decreased E-cadherin expression occurring in many TCC, often as a consequence of promoter hypermethylation, may confer inappropriate responsiveness to WNT factors.

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“…Subsequent gene events involve both oncosuppressor genes linked to apoptosis and the cell cycle, such as p53 mutations on chromosome 17 (Fujimoto et al, 1992) and Rb on chromosome 13 (Wada et al, 2000), and oncogenes involved in signal transduction, such as Ras (Shinohara and Koyanagi, 2002). Besides these hot spots, other chromosomal sites on chromosome 7 (EGFR) (Gazzaniga et al, 2001), chromosome 3 (RAF-1) (Simon et al, 2001), chromosome 8 (C-MYC, FGFR-1) (Christoph et al, 1999;Simon et al, 2001) and other chromosomes are often involved in bladder cancer (Sandberg, 2002). Moreover, epigenetic events of gene amplification lead to hyperexpression of crucial TCC genes, and comparative genomic hybridization (CGH) has recently made it possible to report the amplification of the chromosomal region 12q13-15 (Simon et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Hyperexpression of locus C genes in the HOX network is strongly associated in vivo with human bladder transitional cell carcinomas

et al. 2003

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Bladder carcinogenesis remains unclear despite the identification of chemical, environmental and genetic factors. It has recently been reported that the chromosomal region 12q13-q15, containing crucial cancer genes such as MDM2, CDK4 and GLI, is amplified in bladder cancer. In the same region are also located the genes of the locus HOX C, flanked by keratin genes whose protein product may be a prognostic marker of bladder cancer. The HOX genes constitute a network of transcription factors controlling embryonal development and play an important role in crucial adult eukaryotic cell functions. The molecular organization of this 39-gene network is unique in the genome and probably acts by regulating phenotypical cell identity. We have analysed the expression of the whole HOX gene network in pairs of normaltumour bladder and in tumoral biopsies. Comparison between normal urothelium and bladder tumour has identified dramatic variations of expression in a block of three genes (HOX C4, HOX C5 and HOX C6) localized in the HOX C locus on the chromosome 12q13 and in the paralogous group 11 HOX genes, involved during normal development in the formation of the urogenital system. These data suggest a key involvement of the HOX gene network, and especially the locus C, in bladder cancer.

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Over-expression and amplification of the c-myc gene in human urothelial carcinoma

Cited by 41 publications

References 17 publications

c-MYC Activation in Primary and Metastatic Ductal Adenocarcinoma of the Pancreas: Incidence, Mechanisms, and Clinical Significance

c-MYC Activation in Primary and Metastatic Ductal Adenocarcinoma of the Pancreas: Incidence, Mechanisms, and Clinical Significance

E-cadherin involved in inactivation of WNT/β-catenin signalling in urothelial carcinoma and normal urothelial cells

Hyperexpression of locus C genes in the HOX network is strongly associated in vivo with human bladder transitional cell carcinomas

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