Identification of estrogen receptor-related receptor gamma as a direct transcriptional target of angiogenin.

ABSTRACT: Nuclear translocation of angiogenin (ANG) is essential for the proliferation of its target cells. ANG promotes rRNA synthesis, while whether it regulates mRNA transcription remains unknown. Using the chromatin immunoprecipitation method, we have identified 12 ANG-binding sequences. One of these sequences lies in the estrogen receptor-related receptor gamma (ERR?) gene which we designated as ANG-Binding Sequence within ERR? (ABSE). ABSE exhibited ANG-dependent repressor activity in the luciferase reporter system. Down-regulation of ANG increased ERR? expression, and active gene marker level at the ABSE region. The expression levels of ERR? targets genes, p21(WAF/CIP) and p27(KIP1), and the occupation of ERR? on their promoter regions were increased in ANG-deficient cells accordingly. Furthermore, knockdown of ERR? promoted the proliferation rate in ANG-deficient breast cancer cells. Finally, immunohistochemistry staining showed negative correlation between ANG and ERR? in breast cancer tissue. Altogether, our study provides evidence that nuclear ANG directly binds to the ABSE of ERR? gene and inhibits ERR? transcription to promote breast cancer cell proliferation.

SUBMITTER: Ang J 

PROVIDER: S-EPMC3744552 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature