Anticancer effects on TACC3 by treatment of paclitaxel in HPV-18 positive cervical carcinoma cells.
Previously, we used proteome analysis to identify transforming acidic coiled coil (TACC) 3 as a protein that is down-regulated upon paclitaxel treatment in cervical cancer cells. TACC3 mRNA and protein levels decreased after paclitaxel treatment in a time- and dose-dependent manner, and the transactivation of TACC3 promoter was dramatically diminished by paclitaxel. Importantly, paclitaxel treatment and knockdown of TACC3 by siRNA led to a synergistic enhancement of significant G2/M phase arrest and apoptosis in HeLa cells. In contrast to TACC3-deficient cells, paclitaxel treatment of mTACC3-overexpressing cells failed to induce G2/M phase arrest, cell growth inhibition, and apoptotic cell death. We studied the associated gene in mTACC overexpressed cells using microarray. From these results, numerous genes have been identified as being associated with tumor progression (Ppia, TMSB10, Annexin A2, rab31, prostaglandin E2-EP2, UHRF1), chemoresistance (Akt, Plk-1, MAP kinase) and metastasis (MMP9, PECAM-1) in mTACC3 overexpressed HeLa cells. Thus, TACC3 is thought to be the critical molecule in mediating the anticancer mechanisms of paclitaxel in p53 inactivated cells by inducing G2/M arrest and apoptosis. And our data suggested that the overexpression of TACC3 may be associated with the mechanisms of chemoresistance, tumor progression, cell proliferation and metastasis.
Yim
Eun-Kyoung
EK
Department of Obstetrics and Gynecology, The Catholic University of Korea, Seoul 137-040, Korea.
Tong
Seo-Yun
SY
Ho
Eun-Mi
EM
Bae
Jeong-Hoon
JH
Um
Soo-Jong
SJ
Park
Jong-Sup
JS
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D052161:Human papillomavirus 18; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000187:drug effects* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000494:pharmacology*; D030361:Papillomavirus Infections / Q000150:complications; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000821:virology
D000972:Antineoplastic Agents, Phytogenic; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C120551:TACC3 protein, human; D017239:Paclitaxel