title: BTG1 expression correlates with pathogenesis, aggressive behaviors and prognosis of gastric cancer: a potential target for gene therapy.
abstract: Here, we found that BTG1 overexpression inhibited proliferation, migration and invasion, induced G2/M arrest, differentiation, senescence and apoptosis in BGC-823 and MKN28 cells (p < 0.05). BTG1 transfectants showed a higher mRNA expression of Cyclin D1 and Bax, but a lower mRNA expression of cdc2, p21, mTOR and MMP-9 than the control and mock (p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG1 transfectants showed lower mRNA viability and higher apoptosis than the control in both time- and dose-dependent manners (p < 0.05) with the hypoexpression of chemoresistance-related genes (slug, CD147, GRP78, GRP94, FBXW7 TOP1, TOP2 and GST-π). BTG1 expression was restored after 5-aza-2'-deoxycytidine treatment in gastric cancer cells. BTG1 expression was statistically lower in gastric cancer than non-neoplastic mucosa and metastatic cancer in lymph node (p < 0.05). BTG1 expression was positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, TNM staging and worse prognosis (p < 0.05). The diffuse-type carcinoma showed less BTG1 expression than intestinal- and mixed-type ones (p < 0.05). BTG1 overexpression suppressed tumor growth and lung metastasis of gastric cancer cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that down-regulated BTG1 expression might promote gastric carcinogenesis partially due to its promoter methylation. BTG1 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer.
authors.affiliation: Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China.
authors.forename: Hua-chuan
authors.initials: HC
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China.
authors.forename: Dao-fu
authors.initials: DF
authors.lastname: Shen
authors.affiliation: Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China.
authors.forename: Xue-feng
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China.
authors.forename: Ya-zhou
authors.initials: YZ
authors.lastname: Wu
authors.affiliation: School of Health Science, Tokyo University of Technology, Ohta-ku, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
authors.affiliation: Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China.
authors.forename: Hong-zhi
authors.initials: HZ
authors.lastname: Sun
authors.affiliation: Experimental Center, Liaoning Medical University, Jinzhou, China.
authors.forename: Rong-jian
authors.initials: RJ
authors.lastname: Su
authors.affiliation: Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China.
authors.forename: Jun-sheng
authors.initials: JS
authors.lastname: Luo
authors.affiliation: Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China.
authors.forename: Wen-feng
authors.initials: WF
authors.lastname: Gou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016922:Cellular Senescence; D019175:DNA Methylation; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C074086:BTG1 protein, human
keywords: BTG1; carcinogenesis; gastric cancer; gene therapy; pathobiological behaviors