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Expression profiles of cortisol‐inactivating enzyme, 11β‐hydroxysteroid dehydrogenase‐2, in human epidermal tumors and its role in keratinocyte proliferation
Author(s) -
Terao Mika,
Itoi Saori,
Murota Hiroyuki,
Katayama Ichiro
Publication year - 2013
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/exd.12075
Subject(s) - cortisone , keratinocyte , 11β hydroxysteroid dehydrogenase type 1 , carcinogenesis , seborrheic keratosis , epidermis (zoology) , cell growth , basal cell carcinoma , endocrinology , medicine , basal (medicine) , biology , enzyme , dehydrogenase , cell culture , cancer , biochemistry , basal cell , anatomy , insulin , genetics
The enzyme 11β‐hydroxysteroid dehydrogenase (11β‐ HSD ) catalyzes the interconversion between hormonally active cortisol and inactive cortisone within cells. There are two isozymes: 11β‐ HSD 1 activates cortisol from cortisone and 11β‐ HSD 2 inactivates cortisol to cortisone. 11β‐ HSD 1 was recently discovered in skin, and we subsequently found that the enzyme negatively regulates keratinocyte proliferation. We verified 11β‐ HSD 1 and 11β‐ HSD 2 expression in benign and malignant skin tumors and investigated the role of 11β‐ HSD in skin tumor pathogenesis. Randomly selected formalin‐fixed sections of skin lesions of seborrheic keratosis ( SK ), squamous cell carcinoma ( SCC ), and basal cell carcinoma ( BCC ) were stained with 11β‐ HSD 1 and 11β‐ HSD 2 antibodies, and 11β‐ HSD expression was also evaluated in murine epidermis in which hyperproliferation was induced by 12‐O‐tetradecanoylphorbol‐13 acetate ( TPA ). We observed that 11β‐ HSD 1 expression was decreased in all SK , SCC , and BCC lesions compared with unaffected skin. Conversely, 11β‐ HSD 2 expression was increased in SK and BCC but not in SCC . Overexpression of 11β‐ HSD 2 in keratinocytes increased cell proliferation. In the murine model, 11β‐ HSD 1 expression was decreased in TPA ‐treated hyperproliferative skin. Our findings suggest that 11β‐ HSD 1 expression is decreased in keratinocyte proliferative conditions, and 11β‐ HSD 2 expression is increased in basal cell proliferating conditions, such as BCC and SK . Assessing 11β‐ HSD 1 and 11β‐ HSD 2 expression could be a useful tool for diagnosing and characterizing skin tumors.