KIT (c-kit oncogene product) pathway is constitutively activated in human testicular germ cell tumors.
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| Abstract |
We investigated the expression of KIT (product of c-kit oncogene), gain-of-function mutations, and activation of its downstream signal transduction in human testicular cancers. KIT was expressed in 88% (22/25) of seminomas and in 44.4% (4/9) of non-seminomas compared to adjacent normal testicular tissue. Nine of the KIT-expressing seminomas had mutations (40.9%; 9/22) in the c-kit gene; two cases in exon 11 and 7 cases in exon 17. Two of these mutations in exon 17 were novel, and the other seven mutations were identical to the already known gain-of-function mutations which cause activation of KIT without ligand stem cell factor. All of the mutant KIT and 53.8% (7/13) of wild-type KIT were phosphorylated (activated) and associated with phosphorylated phosphatidylinositol 3-kinase (PI3K). Akt was also phosphorylated in these seminomas, suggesting that the KIT-PI3K-Akt pathway is activated in seminoma. These findings suggest that the KIT-PI3K-Akt pathway is constitutively activated in testicular germ cell tumors, due to overexpression of KIT protein and/or gain-of-function mutations in the c-kit gene.
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| Authors | Yasutomo Nakai, Norio Nonomura, Daizo Oka, Masayuki Shiba, Yasuyuki Arai, Masashi Nakayama, Hitoshi Inoue, Kazuo Nishimura, Katsuyuki Aozasa, Yoichi Mizutani, Tsuneharu Miki, Akihiko Okuyama |
| Journal | Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 337 Issue 1 Pg. 289-96 (Nov 11 2005) ISSN: 0006-291X [Print] United States |
| PMID | 16188233 (Publication Type: Journal Article) |
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