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[Role of Ca v 3.2 T-type Ca 2+ channels in prostate cancer cells].
- Source :
-
Nihon yakurigaku zasshi. Folia pharmacologica Japonica [Nihon Yakurigaku Zasshi] 2019; Vol. 154 (3), pp. 97-102. - Publication Year :
- 2019
-
Abstract
- Among voltage-gated Ca <superscript>2+</superscript> channels, T-type Ca <superscript>2+</superscript> channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells. Among three isoforms of T-type Ca <superscript>2+</superscript> channels, Ca <subscript>v</subscript> 3.2 is detectable in 100% of biopsy samples from prostate cancer patients. In general, prostate cancer cells are highly sensitive to androgen deprivation therapy, but often acquire hormone-therapy resistance. The androgen deprivation may trigger neuroendocrine (NE)-like differentiation of some prostate cancer cells. We have analyzed the expression and function of Ca <subscript>v</subscript> 3.2 in human prostate cancer LNCaP cells during NE-like differentiation. NE-like LNCaP cells overexpress Ca <subscript>v</subscript> 3.2 through the CREB/Egr-1 pathway and also cystathionine-γ-lyase (CSE), which generates H <subscript>2</subscript> S that enhances the channel activity of Ca <subscript>v</subscript> 3.2. H <subscript>2</subscript> S generated by upregulated CSE appears to enhance the activity of upregulated Ca <subscript>v</subscript> 3.2 after the differentiation. The enhanced Ca <subscript>v</subscript> 3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells. It is known that increased extracellular glucose levels enhance Ca <subscript>v</subscript> 3.2 activity through asparagine (N)-linked glycosylation of Ca <subscript>v</subscript> 3.2, which might contribute to diabetic neuropathy. We then found that high glucose accelerates the enhanced channel function and overexpression of Ca <subscript>v</subscript> 3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance. Thus, Ca <subscript>v</subscript> 3.2 is considered to play a role in the pathophysiology of prostate cancer, and may serve as a therapeutic target.
Details
- Language :
- Japanese
- ISSN :
- 0015-5691
- Volume :
- 154
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nihon yakurigaku zasshi. Folia pharmacologica Japonica
- Publication Type :
- Academic Journal
- Accession number :
- 31527367
- Full Text :
- https://doi.org/10.1254/fpj.154.97