CREB inhibits AP-2alpha expression to regulate the malignant phenotype of melanoma.

ABSTRACT:

Background

The loss of AP-2alpha and increased activity of cAMP-responsive element binding (CREB) protein are two hallmarks of malignant progression of cutaneous melanoma. However, the molecular mechanism responsible for the loss of AP-2alpha during melanoma progression remains unknown.

Methodology/principal findings

Herein, we demonstrate that both inhibition of PKA-dependent CREB phosphorylation, as well as silencing of CREB expression by shRNA, restored AP-2alpha protein expression in two metastatic melanoma cell lines. Moreover, rescue of CREB expression in CREB-silenced cell lines downregulates expression of AP-2alpha. Loss of AP-2alpha expression in metastatic melanoma occurs via a dual mechanism involving binding of CREB to the AP-2alpha promoter and CREB-induced over

SUBMITTER: Melnikova VO 

PROVIDER: S-EPMC2929203 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature