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Expression of insulin‐like growth factor‐1 receptor, p‐AKT and p‐ERK1/2 protein in extramammary Paget's disease
Author(s) -
Liu H.,
Moroi Y.,
Yasumoto S.,
Kokuba H.,
Imafuku S.,
Koga T.,
Masuda T.,
Tu Y.,
Furue M.,
Urabe K.
Publication year - 2006
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2006.07366.x
Subject(s) - extramammary paget's disease , medicine , paget disease , protein kinase b , endocrinology , insulin like growth factor , receptor , cancer research , growth factor , disease , biology , signal transduction , microbiology and biotechnology
Summary Background The insulin‐like growth factor‐1 (IGF‐1) receptor (R)‐induced phosphatidylinositol 3‐kinase (PI3K)/AKT and mitogen‐activated protein kinase (MAPK)/ERK signal transduction cascade, which have critical roles in prevention of apoptosis and regulation of cell cycle progression, plays an important role in tumorigenesis. The expression of IGF‐1R, AKT and ERK1/2 has been described in some human malignancies, but not in extramammary Paget's disease (EMPD). Objectives To study the expression of IGF‐1R, p‐AKT and p‐ERK1/2 in EMPD and to evaluate the relationships among them. Methods Thirty‐six tissue samples of 34 patients with primary EMPD were subjected to immunohistochemical staining for IGF‐1R, p‐AKT and p‐ERK1/2. Results Of thirty‐six EMPD tissue samples, 34, 34 and 28 were positive for IGF‐IR, p‐AKT and p‐ERK1/2 expression, respectively; 27, 23 and 17 of the 36 specimens stained positive for IGF‐IR, p‐AKT and p‐ERK1/2 in more than half of Paget's cells, respectively. There were significant correlations between the IGF‐1R and p‐AKT expression as well as between IGF‐1R and p‐ERK1/2 expression. Taken together, these results indicate that IGF‐1R is overexpressed, and AKT and ERK1/2 are frequently phosphorylated in EMPD. Conclusions Our study shows that the expression of IGF‐1R and the induction of p‐AKT and the p‐ERK1/2 pathway may play an important role in the pathogenesis of EMPD. The IGF‐IR system might be a potential therapeutic target in EMPD.