PIG7/LITAF gene mutation and overexpression of its gene product in extramammary Paget's 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.
Matsumura
Yasuhiro
Y
Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. matsumy@takii.kmu.ac.jp
Matsumura
Yumi
Y
Nishigori
Chikako
C
Horio
Takeshi
T
Miyachi
Yoshiki
Y
D017209:Apoptosis; D002471:Cell Transformation, Neoplastic; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010145:Paget Disease, Extramammary / Q000235:genetics* / Q000503:physiopathology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000494:pharmacology; D015854:Up-Regulation
C118738:LITAF protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53