2001 Fiscal Year Final Research Report Summary
Analysis on hormonal receptors in appendage tumors of skin.
| Project/Area Number |
12670811
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | KANAZAWA UNIVERSITY |
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Principal Investigator |
HATTA Naohito KANAZAWA UNIVERSITY, School of Medicine, Trainer, 医学系研究科, 助手 (30272959)
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| Co-Investigator(Kenkyū-buntansha) |
TAKATA Minoru KANAZAWA UNIVERSITY, School of Medicine, Assistant Professor, 医学系研究科, 助教授 (20154784)
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| Project Period (FY) |
2000 – 2001
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| Keywords | cutaneous tumor / hormonal receptos / melanocortin |
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| Research Abstract |
We have studied melanocortin 5 (MC5) and androgen receptors (AR) expression in skin, and allelic variation at the MC5-R and AR locus in diverse human populations and candidate disease groups including extra-mammary P get's disease (EMPD). MC5-R mRNA and protein were detected in normal skin including the sweat glands, tumor cells of EMPD as well as low level expression in the interfollicular epidermis by RT-PCR and immunohistochemistry. Eighty percent cases of EMPD variably expressed nuclear AR protein. Expression of AR mRNA was confirmed by RT-PCR.
Sequencing of the entire the MC5-R coding region in a range of human populations revealed 1 non-synonymous (F209L) and 4 synonymous changes (ASIA, D108D, S125S, and T248T). No additional mutations were found in patients with acne (n=21), hidradenitis supprativa (n=4) and in sebaceous gland lesions comprising sebaceous nevi, adenomas and hyperplasia (n=13). The variant MC5-R was shown to act in a dose dependent manner to a-MSH stimulation, which did not differ from that of wild type using CAMP assay. We have therefore found no evidence of a causative role for MC5-R in sebaceous gland dysfunction, and in the absence of any association between variation at the locus and disease group, the pathophsyiological role of the MC5-R receptor in man requires further study.
Direct sequencing of exon 2 through exon 8 of AR revealed to mutation in any of 10 tumor samples from advanced stage of EMPD. The present findings showing frequent expression of structurally unaltered AR in an advanced stage of EMPD may provide a rational basis for hormone therapy.
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Research Products
(4 results)
