Elevated estrogen receptor-α in VHL-deficient condition induces microtubule organizing center amplification via disruption of BRCA1/Rad51 interaction.

ABSTRACT: Since loss of VHL is frequently detected early phase genetic event in human renal cell carcinoma, pVHL is assumed to be indispensable for suppression of tumor initiation step. However, induction of HIF-1α, target of pVHL E3 ligase, is more adequate to angiogenesis step after tumor mass formation. Concerning this, it has been reported that pVHL is involved in centrosome location during metaphase and regulates ER-α signaling. Here, we provide the evidences that pVHL-mediated ER-α suppression is critical for microtubule organizing center (MTOC) maintaining and elevated ER-α promotes MTOC amplification through disruption of BRCA1-Rad51 interaction. In fact, numerous MTOC in VHL- or BRCA1-deficient cells are reduced by Fulvestrant, inhibitor of ER-α expression as well as antagonist. In addition

SUBMITTER: Jung YS 

PROVIDER: S-EPMC4309251 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature