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PIG7/LITAF gene mutation and overexpression of its gene product in extramammary Paget's disease
Author(s) -
Matsumura Yasuhiro,
Matsumura Yumi,
Nishigori Chikako,
Horio Takeshi,
Miyachi Yoshiki
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20251
Subject(s) - carcinogenesis , extramammary paget's disease , complementary dna , gene , biology , messenger rna , microbiology and biotechnology , point mutation , gene expression , cancer research , mutation , genetics , pathology , medicine , disease
To identify cancer‐related genes that are involved in the carcinogenesis of extramammary Paget's disease (EMPD), we compared mRNA expression profiles of EMPD lesions and corresponding normal skin using cDNA array. Sixty‐eight genes were highly expressed (>5‐fold) in EMPD lesions compared to normal skin, and 40 genes were expressed less than one‐fifth in EMPD lesions. Among them, PIG7/LITAF mRNA was overexpressed in 3 of 4 EMPD cases. PIG7/LITAF transcription is induced by p53 expression and has been implicated in the p53‐induced apoptotic pathway. Since expression of p53 mRNA and p53 protein was not high in any of the 3 EMPD samples compared to the intact skin of the same patient, we analyzed PIG7/LITAF cDNA mutations among 12 EMPD samples (including the former 4) by PCR‐SSCP. Three samples showed shifted bands (2 had point mutations leading to amino acid substitutions and 1 had a silent mutation). One sample with amino acid substitution overexpressed PIG7/LITAF mRNA in cDNA array analysis and RT‐PCR. PIG7/LITAF mRNA expression is confined to tumor cells in in situ mRNA hybridization analysis. These results indicate that genetic disorder and overexpression of PIG7/LITAF may be involved in EMPD carcinogenesis. © 2004 Wiley‐Liss, Inc.