title: Cyclin A2 and its associated kinase activity are required for optimal induction of progesterone receptor target genes in breast cancer cells.
abstract: A role for the cell cycle protein cyclin A2 in regulating progesterone receptor (PR) activity is emerging. This study investigates the role of cyclin A2 in regulating endogenous PR activity in T47D breast cancer cells by depleting cyclin A2 expression and measuring PR target genes using q-RT-PCR. Targets examined included genes induced by the PR-B isoform more strongly than PR-A (SGK1, FKBP5), a gene induced predominantly by PR-A (HEF1), genes induced via PR tethering to other transcription factors (p21, p27), a gene induced in part via extra-nuclear PR signaling mechanisms (cyclin D1) and PR-repressed genes (DST, IL1R1). Progestin induction of target genes was reduced following cyclin A2 depletion. However, cyclin A2 depletion did not diminish progestin target gene repression. Furthermore, inhibition of the associated Cdk2 kinase activity of cyclin A2 also reduced progestin induction of target genes, while Cdk2 enhanced the interaction between PR and cyclin A2. These results demonstrate that cyclin A2 and its associated kinase activity are important for progestin-induced activation of endogenous PR target genes in breast cancer cells.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Moore
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA; Department of Pathology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Edwards
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA; Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA. Electronic address: nweigel@bcm.edu.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Weigel
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D056751:Cyclin A2 / Q000235:genetics / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D011687:Purines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D000077546:Roscovitine
chemical_list: D056751:Cyclin A2; C466914:NU6102; D011687:Purines; D012333:RNA, Messenger; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D000077546:Roscovitine; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: Cyclin A2; Cyclin dependent kinase 2; Progesterone receptor