Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of colorectal carcinoma from adenomas is recognized as the dominant mechanism of colon carcinogenesis. However, early colon carcinomas are being increasingly detected which have no adenomatous elements in their vicinity, and which, despite their small size, already show submucosal invasion. Such tumours (so-called 'de novo' carcinomas) have renewed consideration of the de novo colorectal carcinogenesis pathway. The goal of this study was to evaluate the expression of tumour suppressor gene p53 and apoptosis control gene bcl-2 in de novo carcinomas, compared with early carcinomas developing in the background of an adenoma (ex-adenoma). Fifty cases each of de novo and ex-adenoma carcinomas (pT1) were studied. p53 expression was significantly higher in the de novo carcinomas than in the ex-adenoma carcinomas (62 per cent vs. 42 per cent), while bcl-2 tended to be weaker in the de novo than in the ex-adenoma carcinomas. These differences' support the concept that de novo carcinomas are a unique pathological entity, with a phenotype reflecting their more aggressive behaviour.
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PMID:Expression of bcl-2 and p53 in de novo and ex-adenoma colon carcinoma: a comparative immunohistochemical study. 895 2

The tumour suppressor gene PTEN/MMAC1, which is mutated or homozygously deleted in glioma, breast and prostate cancer, is mapped to a region of 10q which shows loss of heterozygosity (LOH) in bladder cancer. We screened 123 bladder tumours for LOH in the region of PTEN. In 53 informative muscle invasive tumours (> or = pT2), allele loss was detected in 13 (24.5%) and allelic imbalance in four tumours (overall frequency 32%). LOH was found in four of 60 (6.6%) informative, non-invasive tumours (pTa/pT1). We screened 63 muscle invasive tumours for PTEN mutations by single-strand conformation polymorphism (SSCP) analysis and for homozygous deletion by duplex quantitative polymerase chain reaction (PCR). Two homozygous deletions were identified but no mutations. Of 15 bladder tumour cell lines analysed, three showed homozygous deletion of all or part of the PTEN gene, but none had mutations detectable by SSCP analysis. Our results indicate that PTEN is involved in the development of some bladder tumours. The low frequency of mutation of the retained allele in tumours with 10q23 LOH suggests that there may be another predominant mechanism of inactivation of the second allele, for example small intragenic deletions, that hemizygosity may be sufficient for phenotypic effect, or that there is another target gene at 10q23.
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PMID:Somatic mutation of PTEN in bladder carcinoma. 1036 Jun 73

Clear cell renal cell carcinomas (RCCs) are characterized by a deletion of chromosome 3p, which might result in the inactivation of the FHIT (fragile histidine triad) gene, a putative tumour suppressor gene. To explore the relevance of FHIT aberrations for tumour progression and prognosis in clear cell RCCs, FHIT protein expression was analysed in formalin-fixed tissue from 149 clear cell RCCs by immunohistochemistry. FHIT protein expression was found to be markedly reduced in all RCCs, when compared with adjacent non-neoplastic tubule epithelia. Although remaining below the FHIT levels of normal tubule epithelia, a significant increase of FHIT expression became evident from well (G1) to poorly (G3) differentiated clear cell RCCs (p=0.0001) and from low (pT1) to advanced (pT3) tumour stages (p=0.001). The log-rank test demonstrated a significant inverse correlation (p=0.0074) between FHIT expression and tumour aggressiveness as indicated by patient survival. Cox regression analysis revealed that FHIT expression is an independent prognostic parameter (p=0.0139) in clear cell RCCs. In conclusion, clear cell RCCs show a marked reduction of FHIT protein expression when compared with their putative cells of origin. In contrast to other tumour types, however, loss of FHIT protein expression is significantly less pronounced in poorly differentiated RCCs or advanced tumour stages. This versatility of FHIT expression during tumour progression suggests a role for reversible mechanisms of FHIT inactivation during the initiation and progression of clear cell RCCs.
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PMID:FHIT expression in clear cell renal carcinomas: versatility of protein levels and correlation with survival. 1192 Jul 39