C-MYC overexpression is required for continuous suppression of oncogene-induced senescence in melanoma cells.
C-MYC overexpression is required for continuous suppression of oncogene-induced senescence in melanoma cells.
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C-MYC 过表达是持续抑制癌基因诱导的黑色素瘤细胞衰老所必需的。
DOI：
10.1038/onc.2008.258
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发表时间：
2008-11-06
期刊：
影响因子：
8
通讯作者：
Nikiforov, M. A.
中科院分区：
文献类型：
--
作者：
Zhuang, D.;Mannava, S.;Grachtchouk, V.;Tang, W-H;Patil, S.;Wawrzyniak, J. A.;Berman, A. E.;Giordano, T. J.;Prochownik, E. V.;Soengas, M. S.;Nikiforov, M. A.
Malignant melanomas often harbor activating mutations in BRAF (V600E) or, less frequently, in NRAS (Q61R). Intriguingly, the same mutations have been detected at higher incidences in benign nevi, which are largely composed of senescent melanocytes. Overexpression of BRAFV600E or NRASQ61R in human melanocytes in vitro has been shown to induce senescence, although via different mechanisms. How oncogene-induced senescence is overcome during melanoma progression remains unclear. Here, we report that in the majority of analysed BRAFV600E- or NRASQ61R-expressing melanoma cells, C-MYC depletion induced different yet overlapping sets of senescence phenotypes that are characteristic of normal melanocytes undergoing senescence due to overexpression of BRAFV600E or NRASQ61R, respectively. These senescence phenotypes were p16INK4A- or p53-independent, however, several of them were suppressed by genetic or pharmacological inhibition of BRAFV600E or phosphoino-sitide 3-kinase pathways, including rapamycin-mediated inhibition of mTOR-raptor in NRASQ61R-expressing melanoma cells. Reciprocally, overexpression of C-MYC in normal melanocytes suppressed BRAFV600E-induced senescence more efficiently than NRASQ61R-induced senescence, which agrees with the generally higher rates of activating mutations in BRAF than NRAS gene in human cutaneous melanomas. Our data suggest that one of the major functions of C-MYC overexpression in melanoma progression is to continuous suppress BRAFV600E- or NRASQ61R-dependent senescence programs.
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影响因子：
8.8
作者：
Kraehn GM;Utikal J;Udart M;Greulich KM;Bezold G;Kaskel P;Leiter U;Peter RU
通讯作者：
Peter RU
影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
4.8
作者：
Biroccio, A;Amodei, S;Zupi, G
通讯作者：
Zupi, G
影响因子：
64.5
作者：
LOWE, SW;RULEY, HE;HOUSMAN, DE
通讯作者：
HOUSMAN, DE
影响因子：
10.5
作者：
Grandori, C;Wu, KJ;Mormat, RJ
通讯作者：
Mormat, RJ