title: The PPAR(gamma) K422Q mutation does not contribute to troglitazone inefficiency in colon cancer treatment.
abstract: Peroxisome proliferator-activated receptor gamma (PPAR(gamma)) ligands inhibit cell growth of colorectal cancer cells in most experimental models, but no significant effect could be observed in patients with colorectal cancer. We therefore, screened human colorectal tumors to determine the prevalence of the PPAR(gamma) K422Q loss-of-function mutation, recently identified in 50% of colonic cancer cell lines. A sensitive allele-specific real-time amplification assay was developed and 170 colorectal primary tumors and 12 liver metastasis were analyzed. We did not find the K422Q mutation in any of these samples. We can therefore exclude this alteration as a mechanism of resistance to PPAR(gamma) ligands in patients with colon cancer.
authors.affiliation: INSERM U539, Faculté de Médecine, UFR de Médecine,1 rue Gaston Veil, Nantes cedex 44035, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Bouancheau
authors.forename: Bruno
authors.initials: B
authors.lastname: Buecher
authors.forename: Anne
authors.initials: A
authors.lastname: Jarry
authors.forename: Barbara
authors.initials: B
authors.lastname: Simon
authors.forename: Damien
authors.initials: D
authors.lastname: Masson
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cassagnau
authors.forename: Richard
authors.initials: R
authors.lastname: Hamelin
authors.forename: Christian L
authors.initials: CL
authors.lastname: Laboisse
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bézieau
authors.forename: Marc G
authors.initials: MG
authors.lastname: Denis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002839:Chromans; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077288:Troglitazone