1. Activation of c-MYC and c-MYB proto-oncogenes is associated with decreased apoptosis in tumor colon progression.
- Author
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Greco C, Alvino S, Buglioni S, Assisi D, Lapenta R, Grassi A, Stigliano V, Mottolese M, and Casale V
- Subjects
- Adenocarcinoma metabolism, Adenomatous Polyposis Coli genetics, Adenomatous Polyposis Coli metabolism, Adenomatous Polyposis Coli pathology, Adult, Aged, Aged, 80 and over, Cell Transformation, Neoplastic genetics, Colonic Neoplasms metabolism, Disease Progression, Female, Gene Amplification, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Male, Middle Aged, Proto-Oncogene Mas, Proto-Oncogene Proteins c-bcl-2 biosynthesis, Adenocarcinoma genetics, Adenocarcinoma pathology, Apoptosis genetics, Colonic Neoplasms genetics, Colonic Neoplasms pathology, Genes, myb physiology, Genes, myc physiology
- 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.
- Published
- 2001