Clusterin (CLU) and melanoma growth: CLU is expressed in malignant melanoma and 1,25-dihydroxyvitamin D3 modulates expression of CLU in melanoma cell lines in vitro.
BACKGROUND
The glycoprotein clusterin (CLU) has two known isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, while a secretory form (sCLU) is pro-survival. CLU expression has been associated with tumorigenesis and the progression of various malignancies.


METHODS
The expression of CLU was studied immunohistochemically in paraffin sections of primary cutaneous malignant melanomas, metastases of malignant melanomas and acquired melanocytic naevi. Using PCR and Western blotting, the expression of CLU was also investigated in various vitamin D-responsive (MeWo, SK-MEL-28) and vitamin D-resistant melanoma cell lines (SK-MEL-5, SK-MEL-25), as well as in normal human melanocytes (NHM), along with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] treatment.


RESULTS
In contrast to acquired melanocytic naevi, CLU immunoreactivity was found in primary cutaneous malignant melanomas and metastases of malignant melanomas in situ. Both CLU protein and RNA were detected in melanoma cell lines and NHM. Treatment with 1,25(OH)2D3 modulated CLU's expression in vitamin D-responsive but not in -resistant melanoma cell lines.


CONCLUSIONS
CLU may be of importance for the progression of malignant melanoma. The growth regulatory effects of 1,25(OH)2D3 in melanoma cell lines may, at least in part, be mediated via modulation of CLU expression.
Shannan
B
B
Department of Dermatology, The Saarland University Hospital, 66421 Homburg, Germany.
Seifert
M
M
Leskov
K
K
Boothman
D
D
Pföhler
C
C
Tilgen
W
W
Reichrath
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D051152:Clusterin / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000556:secondary
C495242:CLU protein, human; D051152:Clusterin; D002117:Calcitriol