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Vitamin D, clusterin and melanoma growth
Author(s) -
Shannan B.,
Seifert M.,
Tilgen W.,
Reichrath J.
Publication year - 2006
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2006.00439m.x
Subject(s) - clusterin , gene isoform , calcitriol receptor , apoptosis , messenger rna , cell growth , melanoma , alternative splicing , cancer research , microbiology and biotechnology , cell culture , cell cycle , cell , vitamin d and neurology , chemistry , biology , endocrinology , gene , biochemistry , genetics
The secretory glycoprotein clusterin (CLU) was shown to be involved in the regulation of various cell functions including cell growth and apoptosis. The nuclear (nCLU) and the secretory (sCLU) are two isoforms of CLU that are obtained by alternate splicing. While the pro‐apoptotic nCLU was shown to be involved in the regulation of cell‐cycle progression and apoptosis, sCLU has been shown to have cytoprotective properties. We have analyzed the expression of CLU (mRNA and protein) in various melanoma cell lines that have previously been characterized as sensitive (SK‐MEL‐28 and MeWo) or resistant (SK‐MEL‐5, SK‐MEL‐25) to antiproliferative effects of vitamin D analogues. Vitamin D‐resistant melanoma cell lines were shown to reveal a functional defect in vitamin D receptor‐mediated gene transcription. CLU mRNA and protein were present in all melanoma cells analyzed, with sCLU being the most dominant isoform in both vitamin D‐sensitive and resistant cells. 1,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] treatment of vitamin D‐sensitive, but not of resistant, cells resulted in a time‐dependent up‐regulation of CLU mRNA levels, as measured using conventional PCR. Treatment with 1,25(OH) 2 D 3 did neither in vitamin D‐sensitive nor in resistant cells alter the CLU splice variant pattern. Our findings indicate that; CLU is expressed in melanoma cells. sCLU represents the most dominant isoform both in vitamin D‐sensitive and resistant melanoma cells. CLU mRNA expression is increased after 1,25(OH) 2 D 3 treatment in vitamin D‐sensitive but not in resistant melanoma cells. In conclusion, CLU may be of importance for the growth characteristics of melanoma cells. Our findings indicate (at least in melanoma cells) that CLU may be involved in signalling pathways that mediate the antiproliferative effects of 1,25(OH) 2 D 3 .