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| PIK3CA is implicated as an oncogene in ovarian cancer |
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| Author(s): Shayesteh L, Lu YL, Kuo WL, Baldocchi R, Godfrey T, Collins C, Pinkel D, Powell B, Mills GB, Gray JW |
| Source: NATURE GENETICS Volume: 21 Issue: 1 Pages: 99-102 Published: JAN 1999 |
| Times Cited: 599 References: 34 |
| Abstract: Ovarian cancer is the leading cause of death from gynecological malignancy and the fourth leading cause of cancer death among American women(1), yet little is known about its molecular aetiology. Studies using comparative genomic: hybridization (CGH) have revealed several regions of recurrent, abnormal, DNA sequence copy number(2-4) that may encode genes involved in the genesis or progression of the disease. One region at 3q26 found to be increased in copy number in approximately 40% of ovarian(2) and other(5) cancers contains PIK3CA, which encodes the p110 alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3-kinase). The association between PIK3CA copy number and PI3-kinase activity makes PIK3CA a candidate oncogene because a broad range of cancer-related functions have been associated with PI3-kinase mediated signalling(6). These include proliferation(7), glucose transport and catabotism(8), cell adhesion(9), apoptosis(10), RAS signalling6 and oncogenic transformation(11-14). In addition, downstream effecters of Pl3-kinase, AKT1 and AKR, have been found to be amplified(15,16) or activated(17) in human tumours, including ovarian cancer. We show here that PIK3CA is frequently increased in copy number in ovarian cancers, that the increased copy number is associated with increased PIK3CA transcription, p110 alpha protein expression and PO-kinase activity and that treatment with the PI3-kinase inhibitor LY294002 decreases proliferation and increases apoptosis. Our observations suggest PIK3CA is an oncogene that has an important role in ovarian cancer. |
| Document Type: Article |
| Language: English |
| Reprint Address: Gray, JW (reprint author), Univ Calif San Francisco, Ctr Canc, San Francisco, CA USA |
Addresses:
1. Univ Calif San Francisco, Ctr Canc, San Francisco, CA USA
2. Univ Texas, Md Anderson Canc Ctr, Houston, TX 77030 USA
3. Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94702 USA |
| Publisher: NATURE AMERICA INC, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Genetics & Heredity |
| IDS Number: 155RT |
| ISSN: 1061-4036 |
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