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TY - JOUR AU - Vanoverberghe, K. AU - Vanden Abeele, F. AU - Mariot, P. AU - Lepage, G. AU - Roudbaraki, M. AU - Bonnal, J L AU - Mauroy, B. AU - Shuba, Y. AU - Skryma, R. AU - Prevarskaya, N. PY - 2004 DA - 2004/03/01 TI - Ca2+ homeostasis and apoptotic resistance of neuroendocrine-differentiated prostate cancer cells JO - Cell Death & Differentiation SP - 321 EP - 330 VL - 11 IS - 3 AB - Neuroendocrine (NE) differentiation is a hallmark of advanced, androgen-independent prostate cancer, for which there is no successful therapy. NE tumor cells are nonproliferating and escape apoptotic cell death; therefore, an understanding of the apoptotic status of the NE phenotype is imperative for the development of new therapies for prostate cancer. Here, we report for the first time on alterations in intracellular Ca2+ homeostasis, which is a key factor in apoptosis, caused by NE differentiation of androgen-dependent prostate cancer epithelial cells. NE-differentiating regimens, either cAMP elevation or androgen deprivation, resulted in a reduced endoplasmic reticulum Ca2+-store content due to both SERCA 2b Ca2+ ATPase and luminal Ca2+ binding/storage chaperone calreticulin underexpression, and to a downregulated store-operated Ca2+ current. NE-differentiated cells showed enhanced resistance to thapsigargin- and TNF-α-induced apoptosis, unrelated to antiapoptotic Bcl-2 protein overexpression. Our results suggest that targeting the key players determining Ca2+ homeostasis in an attempt to enhance the proapoptotic potential of malignant cells may prove to be a useful strategy in the treatment of advanced prostate cancer. SN - 1476-5403 UR - https://doi.org/10.1038/sj.cdd.4401375 DO - 10.1038/sj.cdd.4401375 ID - Vanoverberghe2004 ER -