PIK3CA as an oncogene in cervical cancer.
Amplification of chromosome arm 3q is the most consistent aberration in cervical cancer, and is implicated in the progression of dysplastic uterine cervical cells into invasive cancer. The present study employed the 'positional candidate gene' strategy to determine the contribution of PIK3CA, which is located in 3q26.3, in cervical tumorigenesis. PIK3CA is known to be involved in the PI 3-kinase/AKT signaling pathway, which plays an important role in regulating cell growth and apoptosis. The results of comparative genomic hybridization show that the 3q26.3 amplification was the most consistent chromosomal aberration in primary tissues of cervical carcinoma, and a positive correlation between an increased copy number of PIK3CA (detected by competitive PCR) and 3q26.3 amplification was found in tumor tissues and in cervical cancer cell lines. In cervical cancer cell lines harboring amplified PIK3CA, the expression of gene product (p110alpha) of PIK3CA was increased, 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 treatment of specific PI 3-kinase inhibitor, suggesting that increased expression of PIK3CA in cervical cancer may result in promoting cell proliferation and reducing apoptosis. These evidences support that PIK3CA is an oncogene in cervical cancer and PIK3CA amplification may be linked to cervical tumorigenesis. Oncogene (2000).
Ma
Y Y
YY
Cancer Research Division, National Health Research Institutes, Taipei, 115, Taiwan.
Wei
S J
SJ
Lin
Y C
YC
Lung
J C
JC
Chang
T C
TC
Whang-Peng
J
J
Liu
J M
JM
Yang
D M
DM
Yang
W K
WK
Shen
C Y
CY
D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division; D002867:Chromones / Q000494:pharmacology; D002893:Chromosomes, Human, Pair 3; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D051058:Oncogene Protein v-akt; D009857:Oncogenes / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D019098:Telomerase / Q000378:metabolism; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism
D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012313:RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D015682:Retroviridae Proteins, Oncogenic; D019098:Telomerase; C422952:telomerase RNA; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one