Abstract B85: Role of the TASK2 in regulating breast cancer cell proliferation

Abstract

Abstract Selective estrogen receptor (ER) modulators (SERMs) such as tamoxifen and raloxifene, and aromatase inhibitors are able to partially reduce incidence in high-risk women to develop ER-positive breast cancer but not all ER-positive neither ER-negative breast cancers. Thus, effective targets and agents for the prevention of both ER-positive and ER-negative breast cancer are urgently needed. Potassium ion channels are essential in maintaining cellular homeostasis in terms of transmitting signal molecules, regulating cell volume and secreting ions and hormones. A family of potassium channels, TASKs, is differentially expressed in normal breast tissue and breast cancer tissues. In particular, TASK2 mRNA was found upregulated in human breast carcinoma but not in normal mammary gland tissue, and TASK2 is significantly up-regulated in ER-negative vs ER-positive breast cancers across multiple studies among the Oncomine databases. We hypothesized that TASK2 plays an important role in regulating growth of breast cancer cells. We then knocked down the TASK2 gene expression using siRNA in ER-positive and ER-negative breast cancer cells. Transient knockdown of TASK2 suppressed cell proliferation significantly in 7/8 ER-negative and moderately in 3/5 ER-positive breast cancer cell lines. However, proliferation of an immortal breast epithelial cell line, MCF-10A, was not affected. We are now investigating the phenotypic alterations in normal and malignant breast cells after overexpressing or knocking down the TASK2 gene. Current results suggest that TASK2 plays an important role in breast cell growth. Thus, TASK2 is a potential novel target for future breast cancer prevention and treatment. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B85.