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Prolactin signals via Stat5 and Oct-1 to the proximal cyclin D1 promoter.

Abstract：

:Prolactin (PRL) modulates proliferation in the mammary gland and other tissues, in part through inducing transcription of cyclin D1, a key regulator of G(1) phase cell cycle progression. We showed previously that PRL, via Jak2, induces binding of Stat5 to a distal GAS site (GAS1) in the cyclin D1 promoter. However, full promoter activity requires additional regions, and in this paper we explored PRL-induced activity at sites other than GAS1. We defined a second PRL-responsive region spanning -254 to -180 that contains a second GAS site (GAS2) and an Oct-1 binding site. Although mutational analysis indicated independence from GAS2, proximal promoter activity remained Stat5-dependent, suggesting alternative mechanisms. EMSA showed that Oct-1 binds the -254 to -180 region and that PRL decreased Oct-1 binding, leading to increased PRL-responsiveness of the proximal cyclin D1 promoter in multiple cell lines. This suggests a role for Oct-1 in PRL-dependent control of cyclin D1 transcription.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Brockman JL,Schuler LA

doi

10.1016/j.mce.2005.04.006

keywords:

subject

Has Abstract

pub_date

2005-07-15 00:00:00

pages

45-53

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(05)00143-7

journal_volume

239

pub_type

杂志文章

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