Human VAT-1: a calcium-regulated activation marker of human epithelial cells.
OBJECTIVE
Human VAT-1 (hVAT-1) is a homologue of the synaptic vesicle membrane protein of Torpedo californica. Its coding gene is located near the BRCA1 locus and thus hVAT-1 may be linked to an inherited predisposition to breast and ovary cancer. However, the hVAT-1 protein expression pattern in normal epithelial tissues such as skin, mammary gland and ovary, as well as in tumours of the mammary gland and ovary, has not been studied.


METHODS
To address this issue, an immunohistological analysis of biopsies of normal epidermis and lesional epidermis of bullous pemphigoid and pemphigus vulgaris patients was undertaken.


RESULTS
hVAT-1-expression was observed in basal keratinocytes of lesional epidermis of bullous pemphigoid patients but not in normal epidermis or in lesional epidermis of pemphigus vulgaris patients. Moreover, hVAT-1 expression in HaCaT cells was found to be calcium-dependent. Normal and malignant mammary and ovary epithelium were found to be hVAT-1-negative.


CONCLUSIONS
Our results indicate that hVAT-1 exerts a specific function in keratinocyte physiology, in particular in calcium-regulated processes, with no evident deregulation in malignancies of the breast and ovary.
Koch
Judith
J
Institute of Immunology, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.
Foekens
John
J
Timmermans
Mieke
M
Fink
Wolfram
W
Wirzbach
Alexander
A
Kramer
Michael D
MD
Schaefer
Birgit M
BM
D000818:Animals; D000911:Antibodies, Monoclonal; D019313:BRCA1 Protein / Q000235:genetics; D015415:Biomarkers; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D018076:DNA, Complementary; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism; D010391:Pemphigoid, Bullous / Q000235:genetics / Q000378:metabolism*; D010392:Pemphigus / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D019313:BRCA1 Protein; D015415:Biomarkers; D018076:DNA, Complementary; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C063277:VAT-1 protein, Torpedo; D002118:Calcium