Abstract
Abstract Current use of selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene, and aromatase inhibitors has reduced breast cancer incidence in high-risk women to develop ER-positive breast cancer. However, a significant portion of ER-positive and all ER-negative breast cancers (both count for ∼60% of all breast cancer) are not prevented with these preventive drugs. Thus, new targets and more effective agents for the prevention of ER-positive and especially ER-negative breast cancer are urgently needed. Ion channels are specific cellular membrane proteins that transport inorganic ions in and out of cells to maintain membrane integrity, cell polarity and cellular homeostasis and may therefore play critical role in transforming normal epithelial cells into malignant cells. The ion channels for transporting Na+, Ca2+, and K+ ions are deregulated in many cancer types including breast cancer. Potassium ion channels are essential in non-excitable cells for regulation of cell volume, secretion of ions and hormones, and are required for maintaining cellular homeostasis. A number of potassium channels such as TASKs, GIRK1, Kca1.1, Kv1.1 and Kv1.3 are differentially expressed in normal breast tissue and breast cancer tissues. We hypothesized that TASKs may be involved in the development of ER-negative breast cancer. We first examined the public microarray databases which contain the mRNA expression profiles from multiple series of human breast cancer samples (http://www.oncomine.org). Transcription of the majority of ion channels for sodium, potassium and calcium were compared in intra-database and inter-database manners. Most of the ion channels show insignificant variations comparing ER-positive versus ER-negative breast cancers. However, TASK2 of the TASKs potassium ion channel family is overexpressed in human breast carcinomas but not in normal mammary gland tissue in three studies. Furthermore, TASK2 is significantly up-regulated in ER-negative vs ER-positive breast cancers in two studies. We then examined expression of TASK2 protein among breast cancer cell lines. TASK2 protein level was undetectable in four ER-positive breast cancer cell lines, while medium/high expression in majority of ER-negative breast cancer cells (all Basal A and Basal B subtypes). We are now investigating the phenotypic alterations in normal and malignant breast cells after overexpressing or knocking down TASK2 gene. Current results suggest that TASK2 may play a role in malignant transformation of breast cells into ER-negative breast cancer cells and maintenance of an ER-negative phenotype. Thus, TASK2 is a potential novel target for future preventive intervention of breast cancer. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B82.
Published Version
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