title: Cyclin D1 determines mitochondrial function in vivo.
abstract: The cyclin D1 gene encodes a regulatory subunit of the holoenzyme that phosphorylates and inactivates the pRb tumor suppressor to promote nuclear DNA synthesis. cyclin D1 is overexpressed in human breast cancers and is sufficient for the development of murine mammary tumors. Herein, cyclin D1 is shown to perform a novel function, inhibiting mitochondrial function and size. Mitochondrial activity was enhanced by genetic deletion or antisense or small interfering RNA to cyclin D1. Global gene expression profiling and functional analysis of mammary epithelial cell-targeted cyclin D1 antisense transgenics demonstrated that cyclin D1 inhibits mitochondrial activity and aerobic glycolysis in vivo. Reciprocal regulation of these genes was observed in cyclin D1-induced mammary tumors. Cyclin D1 thus integrates nuclear DNA synthesis and mitochondrial function.
authors.affiliation: Departments of Cancer Biology, Thomas Jefferson University, BLSB, Room 1050, 233 South 10th Street, Philadelphia, PA 19107, USA.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakamaki
authors.forename: Mathew C
authors.initials: MC
authors.lastname: Casimiro
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ju
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Quong
authors.forename: Sanjay
authors.initials: S
authors.lastname: Katiyar
authors.forename: Manran
authors.initials: M
authors.lastname: Liu
authors.forename: Xuanmao
authors.initials: X
authors.lastname: Jiao
authors.forename: Anping
authors.initials: A
authors.lastname: Li
authors.forename: Xueping
authors.initials: X
authors.lastname: Zhang
authors.forename: Yinan
authors.initials: Y
authors.lastname: Lu
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.forename: Stephen
authors.initials: S
authors.lastname: Byers
authors.forename: Robert
authors.initials: R
authors.lastname: Nicholson
authors.forename: Todd
authors.initials: T
authors.lastname: Link
authors.forename: Melvin
authors.initials: M
authors.lastname: Shemluck
authors.forename: Jianguo
authors.initials: J
authors.lastname: Yang
authors.forename: Stanley T
authors.initials: ST
authors.lastname: Fricke
authors.forename: Phyllis M
authors.initials: PM
authors.lastname: Novikoff
authors.forename: Alexandros
authors.initials: A
authors.lastname: Papanikolaou
authors.forename: Andrew
authors.initials: A
authors.lastname: Arnold
authors.forename: Christopher
authors.initials: C
authors.lastname: Albanese
authors.forename: Richard
authors.initials: R
authors.lastname: Pestell
mesh_terms: D000818:Animals; D001483:Base Sequence; D019938:Cyclin D1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006019:Glycolysis; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050155:Lipogenesis / Q000235:genetics; D008321:Mammary Glands, Animal / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019938:Cyclin D1; D004247:DNA; D006593:Hexokinase