The PPAR(gamma) K422Q mutation does not contribute to troglitazone inefficiency in colon cancer treatment.
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.
Bouancheau
Delphine
D
INSERM U539, Faculté de Médecine, UFR de Médecine,1 rue Gaston Veil, Nantes cedex 44035, France.
Buecher
Bruno
B
Jarry
Anne
A
Simon
Barbara
B
Masson
Damien
D
Cassagnau
Elisabeth
E
Hamelin
Richard
R
Laboisse
Christian L
CL
Bézieau
Stéphane
S
Denis
Marc G
MG
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
D000970:Antineoplastic Agents; D002839:Chromans; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077288:Troglitazone