title: 53BP1 suppresses tumor growth and promotes susceptibility to apoptosis             of ovarian cancer cells through modulation of the Akt pathway.
abstract: 53BP1 has been extensively studied as a key component of the DNA damage response, but little is known regarding the role of 53BP1 in preventing tumor development. The present study was designed to assess the impact of the modification of 53BP1 gene expression on the biological behavior of ovarian cancer cell lines and to elucidate the cellular pathway(s) triggered by 53BP1 in cancer cells. DNA liposome transfection technology was employed to increase and to knock down the expression of 53BP1 in A2780 and HO-8910PM cells, respectively. Viability, clonogenicity and cell cycle profiles were evaluated. Cell apoptosis was analyzed using flow cytometric assay. The expression of proteins related to apoptosis and cell signal transduction was assessed using western blotting. Increased expression of 53BP1 decreased the viability and the clonogenicity, and induced G₂/M arrest and apoptosis of the treated cells. The protein expression of Bax, P21 and caspase-3 was upregulated, while the levels of Bcl-2 and p-Akt were reduced to a statistically significant level. In contrast, deregulation of 53BP1 significantly increased proliferative ability. Collectively, our data suggest that 53BP1 is involved in several important steps in controlling cell proliferation and growth and preventing tumor development.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, PR China.
authors.forename: Shuhui
authors.initials: S
authors.lastname: Hong
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
authors.forename: Beihua
authors.initials: B
authors.lastname: Kong
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000071857:Tumor Suppressor p53-Binding Protein 1; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047908:Intracellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C498301:TP53BP1 protein, human; D025521:Tumor Suppressor Proteins; D000071857:Tumor Suppressor p53-Binding Protein 1; D051028:bcl-2-Associated X Protein; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; D053148:Caspase 3