Abstract A95: KCNK5 regulates proliferation of ER-negative breast cancer cells

Abstract

Abstract Prevention and treatment of estrogen receptor (ER)-negative breast cancer are clinical challenges to reduce breast cancer incidence and mortality. All ER-negative breast cancer and a significant portion of ERpositive breast cancer are not preventable using currently available preventive drugs such as tamoxifen and raloxifene. Furthermore, ER-negative breast cancer does not respond to hormonal therapies and inclines to develop metastasis. Thus, novel targets are urgently needed to achieve effective prevention and treatment of ER-negative breast cancer. The ion channels for transporting potassium ions are deregulated in breast cancers. Specifically, the KCNK5 ion channel is differentially overexpressed at mRNA levels in ERnegative vs ER-positive breast cancers. Several lines of evidence suggest that KCNK5 may be a promising target for ER-negative breast cancer prevention and treatment. We hypothesize that KCNK5 is required for malignant transformation of breast cells and development of ER-negative breast cancer. In our studies, we found that majority of ER-negative breast cancer cells expressed moderate to high level of KCNK5 protein whereas minimal/low levels of KCNK5 in ER-positive cells. We also found that transient knockdown of KCNK5 mRNA with siRNA significantly inhibited proliferation of two ER-negative breast cancer cells (HCC1569 & BT20) that express high levels of KCNK5 protein. We are now testing whether gain of KCNK5 function by overexpressing KCNK5 in ER-negative breast cancer cells (HCC1937 & BT549, expressing relatively low level of KCNK5 protein) will promote cell growth. The proposed studies will provide useful pre-clinical information regarding the role of KCNK5 in ER-negative breast cancer development, which currently is poorly understood. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A95.