title: Inhibitory role of TRIP-Br1 oncoprotein in hypoxia-induced apoptosis in breast cancer cell lines.
abstract: TRIP-Br1 oncoprotein is known to be involved in many vital cellular functions. In this study, we examined the role of TRIP-Br1 in hypoxia-induced cell death. Exposure to the overcrowded and CoCl2-induced hypoxic conditions increased TRIP-Br1 expression at the protein level in six breast cancer cell lines (MCF7, MDA-MB-231, T47D, Hs578D, BT549, and MDA-MB-435) but resulted in no significant change in three normal cell lines (MCF10A, MEF and NIH3T3). Our result revealed that CoCl2-induced hypoxia stimulated apoptosis and autophagy, in which TRIP-Br1 expression was found to be upregulated. Interestingly, TRIP-Br1 silencing in the MCF7 and MDA-MB-231 cancer cells accelerated apoptosis and destabilization of XIAP under the CoCl2-induced hypoxic condition, implying that TRIP-Br1 may render cancer cells resistant to apoptosis through the stabilization of XIAP. We also propose that TRIP-Br1 seems to be upregulated at least partly as a result of the inhibition of PI3K/AKT signaling pathway and the overexpression of HIF-1α. In conclusion, our findings suggest that TRIP-Br1 functions as an oncogenic protein by providing cancer cells resistance to the hypoxia-induced cell death.
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Chengping
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Samil
authors.initials: S
authors.lastname: Jung
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Keun-Il
authors.initials: KI
authors.lastname: Kim
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Chung-Il
authors.initials: CI
authors.lastname: Cheon
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Myeong-Sok
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003035:Cobalt / Q000633:toxicity*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D015854:Up-Regulation; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; C402464:SERTAD1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D003035:Cobalt; C018021:cobaltous chloride