Emerging significance of ER-coregulator PELP1/MNAR in cancer.

The estrogen receptors ERalpha and ERbeta have been implicated in the progression of a wide variety of cancers. The actions of ER are regulated by ER coregulator proteins, including proline-, glutamic acid- and leucine-rich-protein-1 (PELP1/MNAR). PELP1 has been shown to participate in both genomic and nongenomic functions of ER. The expression and localization of PELP1/MNAR are deregulated in a wide variety of tumors and have been implicated in the development of hormonal resistance in cancer cell lines. Emerging data suggest that PELP1/MNAR interacts with many proteins and activates several oncogenes, including Src kinase, phosphotidyl inositol 3 kinase (PI3K), and signal transducers and activators of transcription 3 (STAT3). These new results suggest that PELP1/MNAR may act as an oncogene as well as cooperating with other oncogenes. Thus, PELP1/MNAR may contribute to the tumorigenic potential of cancer cells by serving as a scaffolding protein that couples various signaling complexes with ER.