Titre du document / Document title

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

Auteur(s) / Author(s)

GRECO Claudia ⁽¹⁾ ; ALVINO Silvana ⁽¹⁾ ; BUGLIONI Simonetta ⁽²⁾ ; ASSISI Daniela ⁽³⁾ ; LAPENTA Rocco ⁽³⁾ ; GRASSI Antonio ⁽³⁾ ; STIGLIANO Vittoria ⁽³⁾ ; MOTTOLESE Marcella ⁽²⁾ ; CASALE Vincenzo ⁽³⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Clinical Pathology Service, Regina Elena Cancer Institute, 00100 Rome, ITALIE
⁽²⁾ Pathology Department, Regina Elena Cancer Institute, 00100 Rome, ITALIE
⁽³⁾ Digestive Endoscopy Service, Regina Elena Cancer Institute, 00100 Rome, ITALIE

Résumé / 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.

Revue / Journal Title

Anticancer research   ISSN 0250-7005 

Source / Source

2001, vol. 21, n^o5, pp. 3185-3192 (23 ref.)

Langue / Language

Anglais

Editeur / Publisher

International Institute of Anticancer Research, Attiki, GRECE  (1980) (Revue)

Mots-clés anglais / English Keywords

Genetics ; Digestive diseases ; Intestinal disease ; Colonic disease ; Malignant tumor ; Human ; Tumor progression ; Carcinogenesis ; Cell death ; Apoptosis ; C-Onc gene ; Protooncogene ; Colon ; Adenocarcinoma ;

Mots-clés français / French Keywords

Génétique ; Appareil digestif pathologie ; Intestin pathologie ; Côlon pathologie ; Tumeur maligne ; Gène myb ; Gène myc ; Homme ; Progression carcinogenèse ; Carcinogenèse ; Mort cellulaire ; Apoptose ; Gène onc cellulaire ; Protooncogène ; Côlon ; Adénocarcinome ;

Mots-clés espagnols / Spanish Keywords

Genética ; Aparato digestivo patología ; Intestino patología ; Colón patología ; Tumor maligno ; Hombre ; Progresión carcinogénesis ; Carcinogénesis ; Muerte celular ; Apoptosis ; Gen onc celular ; Protooncogen ; Colón ; Adenocarcinoma ;

Localisation / Location

INIST-CNRS, Cote INIST : 19426, 35400010217371.0070