title: Vitamin D3 regulates the formation and degradation of gap junctions in androgen-responsive human prostate cancer cells.
abstract: 1α-25(OH)2 vitamin D3 (1-25D), an active hormonal form of Vitamin D3, is a well-known chemopreventive and pro-differentiating agent. It has been shown to inhibit the growth of several prostate cancer cell lines. Gap junctions, formed of proteins called connexins (Cx), are ensembles of cell-cell channels, which permit the exchange of small growth regulatory molecules between adjoining cells. Cell-cell communication mediated by gap junctional channels is an important homeostatic control mechanism for regulating cell growth and differentiation. We have investigated the effect of 1-25D on the formation and degradation of gap junctions in an androgen-responsive prostate cancer cell line, LNCaP, which expresses retrovirally-introduced Cx32. Connexin32 is expressed by the luminal and well-differentiated cells of normal prostate and prostate tumors. Our results document that 1-25D enhances the expression of Cx32 and its subsequent assembly into gap junctions. Our results further show that 1-25D prevents androgen-regulated degradation of Cx32, post-translationally, independent of androgen receptor (AR)-mediated signaling. Finally, our findings document that formation of gap junctions sensitizes Cx32-expressing LNCaP cells to the growth inhibitory effects of 1-25D and alters their morphology. These findings suggest that the growth-inhibitory effects of 1-25D in LNCaP cells may be related to its ability to modulate the assembly of Cx32 into gap junctions.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Linda
authors.initials: L
authors.lastname: Kelsey
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Parul
authors.initials: P
authors.lastname: Katoch
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Anuttoma
authors.initials: A
authors.lastname: Ray
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Shalini
authors.initials: S
authors.lastname: Mitra
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Souvik
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Ming-Fong
authors.initials: MF
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Parmender P
authors.initials: PP
authors.lastname: Mehta
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002762:Cholecalciferol / Q000494:pharmacology*; D017630:Connexins / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D012176:Retinoids / Q000494:pharmacology; D000097002:Gap Junction beta-1 Protein
chemical_list: D000728:Androgens; D002762:Cholecalciferol; D017630:Connexins; D011944:Receptors, Androgen; D012176:Retinoids; D000097002:Gap Junction beta-1 Protein