title: BTG1 might be employed as a biomarker for carcinogenesis and a target for gene therapy in colorectal cancers.
abstract: Here, BTG1 overexpression inhibited proliferation, induced differentiation, autophagy, and apoptosis in colorectal cancer cells (p<0.05). BTG1 overexpression reduced mitochondrial membrane potential and caused senescence in HCT-116 transfectants (p<0.05). BTG1-induced G2 arrest might be related to Cyclin B1 and Cdc25B hypoexpression in HCT-15 transfectants, while G1 arrest in HCT-116 transfectants overexpressing p21 and p27. BTG1 overexpression decreased the expression of Bcl-2, Bcl-xL, XIAP, Akt1 or survivin and increased the expression of Bax or p53 in colorectal cancer cells. BTG1-induced autophagy was dependent on Beclin-1 expression. BTG1 overexpression might weaken β-catenin pathway in colorectal cancer cells. The chemosensitivity of BTG1 transfectants to paclitaxel, cisplatin, MG132 or SAHA was positively correlated with its apoptotic induction. There was a lower expression level of BTG1 in cancer than matched non-neoplastic mucosa by RT-PCR (p<0.05), while versa for Western blot and immunohistochemical data (p<0.05). BTG1 overexpression significantly suppressed the growth of HCT-15 and HCT-116 via inhibiting proliferation, inducing apoptosis and autophagy in nude mice. Up-regulated BTG1 expression plays an important role in colorectal carcinogenesis as a potential biomarker. BTG1 expression might reverse aggressive phenotypes, so it might be employed as a target of gene therapy for colorectal cancer.
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Science and Technology, Jinzhou Medical University, Jinzhou, China.
authors.forename: Shu-Rui
authors.initials: SR
authors.lastname: Chen
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Dao-Fu
authors.initials: DF
authors.lastname: Shen
authors.affiliation: School of Health Science, Tokyo University of Technology, Nishi-Kamata, Ohta-ku, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
authors.affiliation: Life Science Institute of Jinzhou Medical University, Jinzhou, China.
authors.forename: Rong-Jian
authors.initials: RJ
authors.lastname: Su
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.|Life Science Institute of Jinzhou Medical University, Jinzhou, China.
authors.forename: Hua-Chuan
authors.initials: HC
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D045325:HCT116 Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C495270:CTNNB1 protein, human; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D051176:beta Catenin; C074086:BTG1 protein, human; D048051:p38 Mitogen-Activated Protein Kinases
keywords: BTG1; aggressive phenotypes; carcinogenesis; colorectal cancer; gene therapy