Activation of c-myc and c-myb proto-oncogenes is associated with decreased apoptosis in tumor colon progression

Claudia Greco, Silvana Alvino, Simonetta Buglioni, Daniela Assisi, Rocco Lapenta, Antonio Grassi, Vittoria Stigliano, Marcella Mottolese, Vincenzo Casale

Research output: Contribution to journalArticle

Abstract

Background: An increasing amount of evidence suggests that progression from normal mucosa to colorectal cancer is accompanied by morphological and genetic alterations. Genetic abnormalities affect malignant transformation via a gradual imbalance of normal tissue homeostasis involving programmed cell death (PCD) or apoptosis. Therefore, it has been hypothesized that alterations in apoptosis may contribute to carcinogenesis. The aim of the present work was to investigate the relationship between frequency of spontaneous apoptosis during transition adenoma - to- carcinoma of the colorectal tract and the incidence of activation of c-myc and c-myb proto-oncogenes, involved both in colon tumorigenesis and apoptosis. Materials and Methods: Ninety-five tissue specimens (60 polyps and 35 adenocarcinomas) were removed with autologous normal adjacent mucosa from colon cancer patients. Genomic DNA was extracted and analyzed for both apoptosis frequency (DNA fragmentation assay) and proto-oncogene activation (Southern blot analysis). On the same samples, Bcl-2 protein expression was evaluated by immunohistochemistry. Results: Our results showed that: i) a significant relationship exists between apoptosis and genesis of colorectal cancer since, compared to adenomatous polyps and adjacent normal mucosa, cell death is markedly inhibited in tumors (p =0.01); ii) during colon tumor progression, apoptosis and amplifications of c-myc/c-myb genes are inversely related; iii) Bcl-2 expression is retained in colon tumors even though at a significantly lower level with respect to adenomatous polyps. Conclusion: These results indicate that failure of the normal apoptotic process together with de-regulation of c-myc and c-myb proto-oncogenes might promote the development of colorectal tumors.

Original languageEnglish
Pages (from-to)3185-3192
Number of pages8
JournalAnticancer Research
Volume21
Issue number5
Publication statusPublished - 2001

Keywords

  • Apoptosis
  • Bcl-2
  • c-myb
  • c-myc
  • Colon cancer
  • Tumor progression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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