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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제20권 제3호
- 발행연도
- 2016.5
- 수록면
- 297 - 304 (8page)
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Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC.
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참고문헌 (24)
참고문헌 신청
Kuro-o M / 1997 / Mutation of the mouse klotho gene leads to a syndrome resembling ageing / Nature 390:45~51
Kurosu H / 2005 / Suppression of aging in mice by the hormone Klotho / Science 309:1829~1833
Ichikawa S / 2007 / A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis / J Clin Invest 117:2684~2691
Lee J / 2010 / The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma / Mol Cancer 9:109
Rubinek T / 2012 / Epigenetic silencing of the tumor suppressor klotho in human breast cancer / Breast Cancer Res Treat 133:649~657
Kurosu H / 2005 / Suppression of aging in mice by the hormone Klotho / Science 309:1829~1833
Ichikawa S / 2007 / A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis / J Clin Invest 117:2684~2691
Lee J / 2010 / The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma / Mol Cancer 9:109
Rubinek T / 2012 / Epigenetic silencing of the tumor suppressor klotho in human breast cancer / Breast Cancer Res Treat 133:649~657
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