Title : Involvement of PKA and Sp1 in the induction of p27(Kip1) by tamoxifen.

Pub. Date : 2003 Aug 1

PMID : 12907235






11 Functional Relationships(s)
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1 Involvement of PKA and Sp1 in the induction of p27(Kip1) by tamoxifen. Tamoxifen cyclin dependent kinase inhibitor 1B Homo sapiens
2 We have previously shown that tamoxifen (Tam) inhibits proliferation of estrogen receptor-negative human non-small cell lung cancer cells and this inhibition is associated with induction of p27(Kip1). Tamoxifen cyclin dependent kinase inhibitor 1B Homo sapiens
3 We have previously shown that tamoxifen (Tam) inhibits proliferation of estrogen receptor-negative human non-small cell lung cancer cells and this inhibition is associated with induction of p27(Kip1). Tamoxifen cyclin dependent kinase inhibitor 1B Homo sapiens
4 In this study, we investigated the mechanism by which Tam increases p27(Kip1) expression. Tamoxifen cyclin dependent kinase inhibitor 1B Homo sapiens
5 Because intracellular p27(Kip1) protein level is mainly controlled via posttranslational regulation, we first tested whether Tam might affect protein stability of p27(Kip1). Tamoxifen cyclin dependent kinase inhibitor 1B Homo sapiens
6 We next examined whether Tam enhanced p27(Kip1) expression through transcriptional activation. Tamoxifen cyclin dependent kinase inhibitor 1B Homo sapiens
7 Our results demonstrated that Tam directly stimulated the p27(Kip1) promoter in lung cancer cells. Tamoxifen cyclin dependent kinase inhibitor 1B Homo sapiens
8 Deletion and mutation analysis revealed that two Sp1 consensus sites located between -545 and -532bp from the transcription start site were crucial for the induction of p27(Kip1) by Tam. Tamoxifen cyclin dependent kinase inhibitor 1B Homo sapiens
9 Our data also demonstrated that induction of p27(Kip1) by Tam was inhibited by protein kinase A inhibitor H89, but not by protein kinase C inhibitor calphostin C and mitogen-activated kinase kinase inhibitor PD98059. Tamoxifen cyclin dependent kinase inhibitor 1B Homo sapiens
10 Taken together, our results suggest that Tam transcriptionally activates p27(Kip1) expression via the Sp1 consensus sites in the p27(Kip1) promoter and PKA is involved in this process. Tamoxifen cyclin dependent kinase inhibitor 1B Homo sapiens
11 Taken together, our results suggest that Tam transcriptionally activates p27(Kip1) expression via the Sp1 consensus sites in the p27(Kip1) promoter and PKA is involved in this process. Tamoxifen cyclin dependent kinase inhibitor 1B Homo sapiens