Abstract
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.
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References
Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ and Cheng JQ . (2002). J. Biol. Chem., 277, 35364–35370.
Eker R and Mossige J . (1961). Nature, 189, 858–859.
Gao X and Pan D . (2001). Genes Dev., 15, 1383–1392.
Gao X, Zhang Y, Arrazola P, Hino O, Kobayashi T, Yeung RS, Ru B and Pan D . (2002). Nat. Cell Biol., 4, 699–704.
Hino O, Klein-Szanto AJ, Freed JJ, Testa JR, Brown DQ, Vilensky M, Yeung RS, Tartof KD and Knudson AG . (1993). Proc. Natl. Acad. Sci. USA, 90, 327–331.
Hino O, Kobayashi T, Tsuchiya H, Kikuchi Y, Kobayashi E, Mitani H and Hirayama Y . (1994). Biochem. Biophys. Res. Commun., 203, 1302–1308.
Hino O, Okimoto K, Kouchi M and Sakurai J . (2001). Jpn. J. Cancer Res., 92, 1147–1149.
Hino O, Kobayashi T, Momose S, Kikuchi Y, Adachi H and Okimoto K . (2003). Cancer Sci., 94, 142–147.
Inoki K, Li Y, Zhu T, Wu J and Guan KL . (2002). Nat. Cell Biol., 4, 648–657.
Kenerson HL, Aicher LD, True LD and Yeung RS . (2002). Cancer Res., 62, 5645–5650.
Kobayashi T, Adachi H, Mitani H, Hirayama Y and Hino O . (2003). Proc. Jpn. Acad., 79, 22–25.
Kobayashi T, Hirayama Y, Kobayashi E, Kubo Y and Hino O . (1995). Nat. Genet., 9, 70–74.
Kobayashi T, Minowa O, Kuno J, Mitani H, Hino O and Noda T . (1999). Cancer Res., 59, 1206–1211.
Kobayashi T, Minowa O, Sugitani Y, Takai S, Mitani H, Kobayashi E, Noda T and Hino O . (2001). Proc. Natl. Acad. Sci. USA, 98, 8762–8767.
Kon S, Maeda M, Segawa T, Hagiwara Y, Horikoshi Y, Chikuma S, Tanaka K, Rashid MM, Inobe M, Chambers AF and Uede T . (2000). J. Cell Biochem., 77, 487–498.
Kubo Y, Klimek F, Kikuchi Y, Bannasch P and Hino O . (1995). Cancer Res., 55, 989–990.
Majima S, Kajino K, Fukuda T, Otsuka F and Hino O . (2000). Jpn. J. Cancer Res., 91, 869–874.
Manning BD, Tee AR, Logsdon MN, Blenis J and Cantley LC . (2002). Mol. Cell, 10, 151–162.
Okimoto K, Kouchi M, Kikawa E, Toyosawa K, Koujitani T, Tanaka K, Matsuoka N, Sakurai J and Hino O . (2000). Jpn. J. Cancer Res., 91, 1096–1099.
Potter CJ, Huang H and Xu T . (2001). Cell, 105, 357–368.
Takahashi R, Hirabayashi M, Yanai N, Obinata M and Ueda M . (1999). Exp. Anim., 48, 255–261.
Tapon N, Ito N, Dickson BJ, Treisman JE and Hariharan IK . (2001). Cell, 105, 345–355.
Yeung RS, Xiao GH, Jin F, Lee WC, Testa JR and Knudson AG . (1994). Proc. Natl. Acad. Sci. USA, 91, 11413–11416.
Acknowledgements
We thank Drs K Okimoto (Nihon rats) and R Takahashi (SV40 large T antigen transgenic rats) for making available unpublished data. We also thank Dr I Fukui for supplying human samples. This work is supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Culture, Sports and Science Technology of Japan and the Ministry of Health, Labour and Welfare of Japan.
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Adachi, H., Majima, S., Kon, S. et al. Niban gene is commonly expressed in the renal tumors: a new candidate marker for renal carcinogenesis. Oncogene 23, 3495–3500 (2004). https://doi.org/10.1038/sj.onc.1207468
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DOI: https://doi.org/10.1038/sj.onc.1207468
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