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Mutations in PIK3CA sensitize breast cancer cells to physiologic levels of aspirin.

Abstract：

:A review of the literature finds that women diagnosed with breast cancer, who were on an aspirin regimen, experienced a decreased risk of distant metastases and death. Several recent studies have reported an improvement in overall survival in colorectal cancer patients who harbored mutations in the oncogene PIK3CA and received a daily aspirin regimen. Breast cancer patients on a daily aspirin regimen experienced decreased risk of distant metastases and death. PIK3CA is the most frequently mutated oncogene in breast cancer, occurring in up to 45 % of all breast cancers. In order to determine if mutations in PIK3CA sensitized breast cancers to aspirin treatment, we employed the use of isogenic cellular clones of the non-tumorigenic, breast epithelial cell line MCF-10A that harbored mutations in either PIK3CA or KRAS or both. We report that mutations in both PIK3CA and KRAS are required for the greatest aspirin sensitivity in breast cancer, and that the GSK3β protein was hyperphosphorylated in aspirin-treated double knockin cells, but not in other clones/treatments. A more modest effect was observed with single mutant PIK3CA, but not KRAS alone. These observations were further confirmed in a panel of breast cancer cell lines. Our findings provide the first evidence that mutations in PIK3CA sensitize breast cancer cells to aspirin.

journal_name

Breast Cancer Res Treat

journal_title

Breast cancer research and treatment

authors

Turturro SB,Najor MS,Ruby CE,Cobleigh MA,Abukhdeir AM

doi

10.1007/s10549-016-3729-8

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

33-43

issue

1

eissn

0167-6806

issn

1573-7217

pii

10.1007/s10549-016-3729-8

journal_volume

156

pub_type

杂志文章

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