title: RASSF10 suppresses colorectal cancer growth by activating P53 signaling and sensitizes colorectal cancer cell to docetaxel.
abstract: RASSF10 has previously been reported to be frequently methylated in a number of malignancies. To understand the importance of RASSF10 inactivation in colorectal carcinogenesis, eight colorectal cancer cell lines, 89 cases of primary colorectal cancer and 5 cases of normal colorectal mucosa were examined. Methylation specific PCR, western blot, siRNA, gene expression array and xenograft mice were employed. The expression of RASSF10 was regulated by promoter regional methylation in colorectal cancer cells. RASSF10 was methylated in 60.7% (54/89) of primary colorectal cancers and was positively associated with tumor stage (p < 0.05) and metastasis (p < 0.05). Restoration of RASSF10 led to inhibition of colorectal cancer cell proliferation in vitro and in vivo and increased apoptosis. Gene expression arrays discovered RASSF10 inhibition of MDM2 expression as a mediator of these effects, which was confirmed with RT-PCR and western blot. RASSF10 was shown to activate P53 signaling in RKO and HCT116 cells after UV exposure, and sensitized these cells to docetaxel. In conclusion, our study demonstrates RASSF10 is frequently methylated in human colorectal cancer leading to loss of expression. RASSF10 normally suppresses human colorectal cancer growth by activating P53 signaling in colorectal cancer, and restored expression sensitizes colorectal cancer to docetaxel.
authors: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing 100853, P.R.China.
authors: Jing
authors: J
authors: Guo
authors: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing 100853, P.R.China.|Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R.China.
authors: Yage
authors: Y
authors: Yang
authors: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing 100853, P.R.China.
authors: Yunsheng
authors: Y
authors: Yang
authors: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing 100853, P.R.China.
authors: Enqiang
authors: E
authors: Linghu
authors: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, P.R.China.
authors: Qimin
authors: Q
authors: Zhan
authors: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland 21231, U.S.A.
authors: Malcolm V
authors: MV
authors: Brock
authors: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland 21231, U.S.A.
authors: James G
authors: JG
authors: Herman
authors: Department of Gastroenterology and Hepatology, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R.China.
authors: Bingyong
authors: B
authors: Zhang
authors: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing 100853, P.R.China.
authors: Mingzhou
authors: M
authors: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D000077143:Docetaxel; D044127:Epigenesis, Genetic; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000502:physiology; D016158:Genes, p53; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000494:pharmacology*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C548440:RASSF10 protein, human; C495901:TP53 protein, human; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D000077143:Docetaxel
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