Bcl-2/Bax protein ratio predicts 5-fluorouracil sensitivity independently of p53 status

• DOI: 10.1054/bjoc.2000.1455
• Publication Date: 2002-07-26T11:27:09Z
• Authors: J-F Mirjolet; M Barberi-Heyob; C Didelot; J-P Peyrat; J Abecassis; R Millon; J-L Merlin
• Keywords: 0301 basic medicine; Dose-Response Relationship, Drug; Carcinoma; Cell Cycle; Regular Article; Apoptosis; Breast Neoplasms; Adenocarcinoma; Genes, p53; Up-Regulation; 3. Good health; Gene Expression Regulation, Neoplastic; Pancreatic Neoplasms; 03 medical and health sciences; Proto-Oncogene Proteins c-bcl-2; Head and Neck Neoplasms; Proto-Oncogene Proteins; Tumor Cells, Cultured; Humans; Female; Fluorouracil; RNA, Messenger; bcl-2-Associated X Protein

p53 tumour-suppressor gene is involved in cell growth control, arrest and apoptosis. Nevertheless cycle apoptosis induction can be observed p53-defective cells after exposure to DNA-damaging agents such as 5-fluorouracil (5-FU) suggesting the importance of alternative pathways via p53-independent mechanisms. In order establish relationship between status, arrest, Bcl-2/Bax regulation 5-FU sensitivity, we examined mRNA protein expression functionality wild-type (wt) mutant (mt) lines. were determined before equitoxic concentration six human carcinoma lines differing status displaying marked differences with IC(50)values ranging from 0.2-22.6 mM. induced a rise mt papilloma virus positive wt line, whereas significant decrease was found line. Whatever altered transcriptional translational leading up-regulation protein. relation functionality, but independently mutational concentration, all able G1. No evidenced G1 accumulation ability sensitivity. Moreover, exposure, Bax Bcl-2 proteins under control statistically (r = 0.880, P 0.0097) ratio conclusion, whatever or correlated