Characterization of beta subunits of voltage sensitive sodium channels in the LNCaP progression model and in the normal mouse prostate

Abstract

Prostate cancer is the alteration of normal prostate cells to aberrant cells that are independent of normal growth and normal regulations that can lead to a metastatic androgen independent phenotype and ultimately death. The cause of prostate cancer is still unknown. A potential set of proteins that play a role in the prostate cancer phenotype are voltage sensitive sodium channels. The alpha subunits of voltage sensitive sodium channels have been shown to play a role in prostate and breast cancer. However, the accessory beta subunits have not been well characterized in cancer or in the normal prostate. Beta subunits could potentially play a role in cancer by modulating and/or trafficking alphas. They may act independent of alpha subunits by acting as adhesion molecules, affecting the migratory ability of cancer cells, or affecting downstream signaling. The cell lines of the LNCaP progression model were used to look at the expression of beta subunits in prostate cancer progression. The lobes of the mouse prostate were used to examine beta expression in the normal prostate. This led to the hypothesis that the Beta subunits were found in increasing levels from the less metastatic and androgen sensitive cell line LNCaP to the more metastatic and less androgen independent cell line C4-2B4 and the beta subunit expression was regulated by androgen. Beta subunits were also located in the three lobes of the normal mouse prostate and there expression was regulated by androgen. It was found that all four beta subunits were found in the cell lines of the LNCaP progression model on either the RNA or Protein level. Beta 1, 3 and 4 were found in the mouse prostate on the protein level. Castration affected the expression pattern of some of the beta subunits in the both the cell lines of the LNCaP progression model and in the mouse prostate; this indicated that beta expression may be regulated by androgen in the prostate. The implications for the altered expression of beta subunits are that they could play a role in prostate cancer.