TY - JOUR
T1 - 17β-Estradiol rapidly stimulates c-fos expression via the MAPK pathway in T84 cells
AU - Hennessy, Barbara A.
AU - Harvey, Brian J.
AU - Healy, Vincent
PY - 2005/1/14
Y1 - 2005/1/14
N2 - In this study, we show that 17β-Estradiol (E2) induced the proliferation of T84 colonic carcinoma cells. We, further, investigated the mechanisms underlying this proliferation and show that E2 induced c-fos protooncogene expression in T84 cells in a timescale consistent with a rapid non-genomic action of the hormone. Furthermore, E2 rapidly phosphorylated both CREB and ELK1, transcription factors that bind to the c-fos promoter and stimulate transcription. Pretreatment with PD98059 and H89, mitogen-activated protein kinase (MAPK) pathway and protein kinase A (PKA) inhibitors, respectively showed that phosphorylation of CREB and ELK1 and subsequent c-fos induction was mediated by the MAPK pathway only. Finally, the estrogen receptor (ER) antagonist, ICI 182,780, blocked the activation of MAPK pathway, subsequent CREB and ELK1 phosphorylation and c-fos induction in T84 cells suggesting an ER dependent mechanism. Consistent with this finding, ICI 182,780 caused a substantial reduction in the proliferative effects of E2 on T84 cells.
AB - In this study, we show that 17β-Estradiol (E2) induced the proliferation of T84 colonic carcinoma cells. We, further, investigated the mechanisms underlying this proliferation and show that E2 induced c-fos protooncogene expression in T84 cells in a timescale consistent with a rapid non-genomic action of the hormone. Furthermore, E2 rapidly phosphorylated both CREB and ELK1, transcription factors that bind to the c-fos promoter and stimulate transcription. Pretreatment with PD98059 and H89, mitogen-activated protein kinase (MAPK) pathway and protein kinase A (PKA) inhibitors, respectively showed that phosphorylation of CREB and ELK1 and subsequent c-fos induction was mediated by the MAPK pathway only. Finally, the estrogen receptor (ER) antagonist, ICI 182,780, blocked the activation of MAPK pathway, subsequent CREB and ELK1 phosphorylation and c-fos induction in T84 cells suggesting an ER dependent mechanism. Consistent with this finding, ICI 182,780 caused a substantial reduction in the proliferative effects of E2 on T84 cells.
KW - 17β-Estradiol
KW - c-fos
KW - Estrogen receptor
KW - MAPK pathway
KW - Western blotting
UR - https://www.scopus.com/pages/publications/10944239132
U2 - 10.1016/j.mce.2004.10.001
DO - 10.1016/j.mce.2004.10.001
M3 - Article
C2 - 15607527
AN - SCOPUS:10944239132
SN - 0303-7207
VL - 229
SP - 39
EP - 47
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -
