Expression of proopiomelanocortin (POMC)-derived melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) peptides in skin of basal cell carcinoma patients.
We proposed that local expression and production of proopiomelanocortin (POMC) peptides may play a role in human skin physiology and pathology, including the development and progression of skin cancers. Reverse transcription polymerase chain reaction (RT-PCR) and Northern blotting hybridization techniques were used to study gene expression. Reversed-phase (RP) high-pressure liquid chromatography (HPLC) separation with subsequent radioimmunoassays were used to identify alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) peptides. Immunocytochemistry (IHC) was used to localize ACTH, alpha-MSH, and beta-MSH antigens in skin. RT-PCR, RP-HPLC, and IHC analyses documented the expression of POMC mRNA and production of ACTH and alpha-MSH peptides in lesional and perilesional skin of basal cell carcinoma (BCC) patients and in cultured keratinocytes, which was accompanied by the expression of the MC1-R gene encoding the receptor activated by MSH and ACTH. Thirty specimens were analyzed by IHC. Immunoreactive alpha-MSH, beta-MSH, and ACTH were detected, in 21 of 21, in 11 of 20, and in 6 of 8 of lesional skin, and in 6 of 6, in 5 of 7, and in 6 of 8 perilesional skin specimens analyzed, respectively. Antigen distribution was heterogenous and present in BCC, epidermis, hair follicles, dermal mononuclear cells, and extracellular matrix. We conclude that messenger RNA for POMC, MC1-R, and the peptides MSH and ACTH are produced in skin of BCC patients. Because keratinocytes are a target for MSH and ACTH bioregulation, the production of these peptides is stimulated by UVB, and the peptides can act as immunosupressors, we suggest that MSH and ACTH may facilitate development of BCC.
Slominski
A
A
Department of Pathology, Loyola University Medical Center, Maywood, IL 60153, USA.
Heasley
D
D
Mazurkiewicz
J E
JE
Ermak
G
G
Baker
J
J
Carlson
J A
JA
D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018043:Receptors, Corticotropin / Q000378:metabolism; D044101:Receptors, Melanocortin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones