Niban gene is commonly expressed in the renal tumors: a new candidate marker for renal carcinogenesis.
Functional inactivation of tuberous sclerosis 2 gene (Tsc2) leads to renal carcinogenesis in the hereditary renal carcinoma Eker rat models. Recent studies revealed a role of tuberin, a TSC2 product, in suppressing the p70 S6 kinase (p70S6K) activity via inhibition of mammalian target of rapamycin (mTOR). Phosphorylated S6 protein, a substrate of p70S6K, was expressed in the early lesions in Eker rats, and this expression was suppressed by the treatment of rapamycin, an inhibitor of mTOR. We previously isolated the novel gene Niban expressed in renal carcinogenesis of Eker rats. In this study, we demonstrated that the expression of Niban was detected from early preneoplastic lesions in Eker rats. Interestingly, in contrast to the phosphorylated S6 protein, the expression of Niban was unchanged and early lesions still remained even after treatment with rapamycin. These results might suggest the existence of another pathway independent of mTOR-S6K pathway in Tsc2 mutant renal carcinogenesis. In addition, Niban was also expressed in other renal carcinoma models, including Tsc1 and Tsc2 knockout mice, and various types of human renal cell carcinomas. Thus, Niban was commonly expressed in renal carcinomas and might be a new marker for renal carcinogenesis.
Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
Hiroyuki
H
Adachi
Shuichi
S
Majima
Shigeyuki
S
Kon
Toshiyuki
T
Kobayashi
Kazunori
K
Kajino
Hiroaki
H
Mitani
Youko
Y
Hirayama
Hiroaki
H
Shiina
Mikio
M
Igawa
Okio
O
Hino
D000595:Amino Acid Sequence; D000818:Animals; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011230:Precancerous Conditions / Q000235:genetics*; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D012097:Repressor Proteins; C000624653:TSC2 protein, human; C000624654:Tsc2 protein, mouse; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus