title: ING4 induces G2/M cell cycle arrest and enhances the chemosensitivity to DNA-damage agents in HepG2 cells.
abstract: The known members of inhibitor of growth (ING) gene family are considered as candidate tumor suppressor genes. ING4, a novel member of ING family, is recently reported to interact with tumor suppressor p53, p300 (a major component of histone acetyl transferase complexes), and p65(RelA) subunit of NF-kappaB. In this study, we investigated the cellular behaviors of HepG2 cells with exogenous ING4. Interestingly, the overexpression of ING4 negatively regulated the cell growth with significant G2/M arrest of cell cycle, and moreover, enhanced the cell apoptosis triggered by serum starvation in HepG2 cells. Furthermore, the exogenous ING4 could upregulate endogenous p21 and Bax in HepG2 cells, not in p53-deficient Saos-2 cells, suggesting that G2/M arrest induced by ING4 could be mediated by the increased p21 expression in a p53-dependent manner, although there is no significant increase of p53 expression in HepG2 cells. Moreover, HepG2 cells with exogenous ING4 could significantly increase cell death, as exposed to some DNA-damage agents, such as etoposide and doxorubicin, implying that ING4 could enhance chemosensitivity to certain DNA-damage agents in HepG2 cells.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Lu-Sheng
authors.initials: LS
authors.lastname: Xu
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Ke-Sheng
authors.initials: KS
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Cheng
authors.forename: Shang-Zhi
authors.initials: SZ
authors.lastname: Huang
authors.forename: Dong-Zhi
authors.initials: DZ
authors.lastname: Wei
authors.forename: Ze-Guang
authors.initials: ZG
authors.lastname: Han
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D016923:Cell Death; D002455:Cell Division; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D016195:G2 Phase; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis; D016328:NF-kappa B / Q000378:metabolism; D016366:Open Reading Frames; D010957:Plasmids / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D013997:Time Factors; D051996:Transcription Factor RelA; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*; D051028:bcl-2-Associated X Protein; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D004247:DNA; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016283:Proto-Oncogene Proteins p21(ras); D051996:Transcription Factor RelA; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C494826:BAX protein, human; C494827:Bax protein, mouse; C483230:ING4 protein, human; C501009:HRAS protein, human