TY - JOUR
T1 - Cyclin A2 and its associated kinase activity are required for optimal induction of progesterone receptor target genes in breast cancer cells
AU - Moore, Nicole L.
AU - Edwards, Dean P.
AU - Weigel, Nancy L.
N1 - Funding Information:
This project was supported by NIH R01CA57539 (to N.L.W.), NIH R01DK49030 (to D.P.E), the Proteomic Shared Resource of the NCI designated Dan L. Duncan Cancer Center at Baylor College of Medicine ( P30CA125123 ) and the BCM Cytometry and Cell Sorting Core with funding from the NIH (NCRR grant S10RR024574 , NIAID AI036211 and NCI P30CA125123 ).
PY - 2014/10
Y1 - 2014/10
N2 - 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.
AB - 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.
KW - A2
KW - Cyclin
KW - Cyclin dependent kinase 2
KW - Progesterone receptor
UR - http://www.scopus.com/inward/record.url?scp=84907476915&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2014.09.009
DO - 10.1016/j.jsbmb.2014.09.009
M3 - Article
C2 - 25220500
AN - SCOPUS:84907476915
SN - 0960-0760
VL - 144
SP - 471
EP - 482
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - PB
ER -