Neuroendocrine differentiation of prostate cancer cells enhances regulatory volume decrease mechanisms, which may contribute to their resistance to apoptosis.
Answers are grounded in this paper and cite their sources.
Preclinical NE differentiation data suggest enhanced apoptosis resistance in prostate cancer; leaves open whether ClC-3 modulation offers clinical targets.
Neuroendocrine (NE) differentiation of prostate epithelial/basal cells is a hallmark of advanced, androgen-independent prostate cancer, for which there is no successful therapy. Here we report for the first time on alterations in regulatory volume decrease (RVD) and its key determinant, swelling-activated Cl- current (I(Cl,swell)), associated with NE differentiation of androgen-dependent LNCaP prostate cancer epithelial cells. NE-differentiating regimens, namely, chronic cAMP elevation or androgen deprivation, resulted in generally augmented I(Cl,swell) and enhanced RVD. This occurred as a result of both the increased endogenous expression of ClC-3, which is a volume-sensitive Cl- channel involved, as we show, in I(Cl,swell) in LNCaP (lymph-node carcinoma of the prostate) cells and the weaker negative I(Cl,swell) control from Ca2+ entering via store-dependent pathways. The changes in the RVD of NE-differentiated cells generally mimicked those reported for Bcl-2-conferred apoptotic resistance. Our results suggest that strengthening the mechanism that helps to maintain volume constancy may contribute to better survival rates of apoptosis-resistant NE cells.
No takes yet. Share an insight, caveat, or question.
Loïc Lemonnier (2005) studied this question.
Synapse has enriched 10 related papers. Consider them for comparative context: