Journal article
Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis
Cancer research (Chicago, Ill.), Vol.72(16), pp.4262-4275
08/15/2012
DOI: 10.1158/0008-5472.CAN-12-0139
PMCID: PMC3614094
PMID: 22665267
Abstract
Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, has emerging roles in cancer. We report here that NAC1 acts as a negative regulator of cellular senescence in transformed and nontransformed cells, and dysfunction of NAC1 induces senescence and inhibits its oncogenic potential. We show that NAC1 deficiency markedly activates senescence and inhibits proliferation in tumor cells treated with sublethal doses of γ-irradiation. In mouse embryonic fibroblasts from NAC1 knockout mice, following infection with a Ras virus, NAC1-/- cells undergo significantly more senescence and are either nontransformed or less transformed in vitro and less tumorigenic in vivo when compared with NAC1+/+ cells. Furthermore, we show that the NAC1-caused senescence blunting is mediated by ΔNp63, which exerts its effect on senescence through p21, and that NAC1 activates transcription of ΔNp63 under stressful conditions. Our results not only reveal a previously unrecognized function of NAC1, the molecular pathway involved and its impact on pathogenesis of tumor initiation and development, but also identify a novel senescence regulator that may be exploited as a potential target for cancer prevention and treatment.
Details
- Title: Subtitle
- Dysfunction of nucleus accumbens-1 activates cellular senescence and inhibits tumor cell proliferation and oncogenesis
- Creators
- Yi Zhang - Department of Pharmacology, College of Pharmaceutical Sciences, Cyrus Tang Hematology Center, Soochow University, Suzhou, JiangSu, ChinaYan ChengXingcong RenTsukasa HoriKathryn J Huber-KeenerLi ZhangKai Lee YapDavid LiuLisa ShantzZheng-Hong QinSuping ZhangJianrong WangHong-Gang WangIe-Ming ShihJin-Ming Yang
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.72(16), pp.4262-4275
- DOI
- 10.1158/0008-5472.CAN-12-0139
- PMID
- 22665267
- PMCID
- PMC3614094
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- United States
- Grant note
- R01CA135038 / NCI NIH HHS R01 CA129682 / NCI NIH HHS R01 CA135038 / NCI NIH HHS R01 CA103937 / NCI NIH HHS R01CA103937 / NCI NIH HHS
- Language
- English
- Date published
- 08/15/2012
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9983931773602771
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