title: Activation of c-MYC and c-MYB proto-oncogenes is associated with decreased apoptosis in tumor colon progression.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Pathology Service, Regina Elena Cancer Institute, Rome, Italy. ayyctg@tin.it
authors.forename: C
authors.initials: C
authors.lastname: Greco
authors.forename: S
authors.initials: S
authors.lastname: Alvino
authors.forename: S
authors.initials: S
authors.lastname: Buglioni
authors.forename: D
authors.initials: D
authors.lastname: Assisi
authors.forename: R
authors.initials: R
authors.lastname: Lapenta
authors.forename: A
authors.initials: A
authors.lastname: Grassi
authors.forename: V
authors.initials: V
authors.lastname: Stigliano
authors.forename: M
authors.initials: M
authors.lastname: Mottolese
authors.forename: V
authors.initials: V
authors.lastname: Casale
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D020570:Genes, myb / Q000502:physiology*; D016259:Genes, myc / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2