PIK3CA as an oncogene in cervical cancer

Amplification of chromosome arm 3q is the most consistent aberration in cer vical cancer, and is implicated in the progression of dysplastic uterine ce rvical cells into invasive cancer. The present study employed the 'position al candidate gene' strategy to determine the contribution of PIK3CA, which is located in 3q26.3, in cervical tumorigenesis, PIK3CA is known to be invo lved in the PI 3-kinase/AKT signaling pathway, which plays an important rol e in regulating cell growth and apoptosis, The results of comparative genom ic hybridization show that the 3q26.3 amplification was the most consistent chromosomal aberration in primary tissues of cervical carcinoma, and a pos itive correlation between an increased copy number of PIK3CA (detected by c ompetitive PCR) and 3q26.3 amplification was found in tumor tissues and in cervical cancer cell lines. In cervical cancer cell lines harboring amplifi ed PIK3CA, the expression of gene product (p110 alpha) of PIK3CA was increa sed, and was subsequently associated with high kinase activity. In addition , transformation phenotypes in these lines, including increased cell growth and decreased apoptosis, were found to be significantly affected by the tr eatment of specific PI 3-kinase inhibitor, suggesting that increased expres sion of PIK3CA in cervical cancer may result in promoting cell proliferatio n and reducing apoptosis, These evidences support that PIK3CA is an oncogen e in cervical cancer and PIK3CA amplification may be linked to cervical tum origenesis.