title: Inhibition of Akt/FOXO3a signaling by constitutively active FOXO3a suppresses growth of follicular thyroid cancer cell lines.
abstract: Akt-dependent FOXO3a cytoplasmic translocation is an important tumorigenic mechanism for escaping from apoptosis in cancer cells. In the present study, we examined whether non-phosphorylatable FOXO3a can inhibit cell growth of various follicular thyroid carcinoma (FTC) cell lines. Adenovirus carrying the FOXO3a-triple mutant (TM) sequence including point mutations at three Akt phosphorylation sites (Ad-FOXO3a-TM) was generated and transduced to the cells to mimic inhibition of Akt/FOXO3a signal. Transduction of Ad-FOXO3a-TM to FTC133 cells induced cell cycle arrest and apoptosis. Injection of Ad-FOXO3a-TM suppressed the growth of xenograft tumors in athymic mice. Consequently, our results indicate that gene therapy based on Ad-FOXO3a-TM has therapeutic potential for FTC.
authors.affiliation: Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Hong
authors.forename: Hyeon Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Dong Yeob
authors.initials: DY
authors.lastname: Shin
authors.forename: Suk Kyoung
authors.initials: SK
authors.lastname: Kim
authors.forename: Miran
authors.initials: M
authors.lastname: Seo
authors.forename: Eun Jig
authors.initials: EJ
authors.lastname: Lee
mesh_terms: D018263:Adenocarcinoma, Follicular; D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015316:Genetic Therapy; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000502:physiology; D013964:Thyroid Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D051057:Proto-Oncogene Proteins c-akt