Androgen actions via androgen receptor promote PTEN inactivation induced uterine cancer.
Mutations in the tumour suppressor phosphatise and tensin homolog (PTEN) result in Cowden syndrome, a rare autosomal dominant inherited disorder characterised by multiple tumour-like growths called hamartomas and an increased risk of developing hormone-dependent cancers. In uterine cancers, PTEN mutations are commonly observed, although what triggers this event remains ill-defined. Although uterine cancers respond strongly to oestrogen and progesterone signalling, how androgens potentially affect these cancers remains poorly defined.
This study examined whether complete androgen receptor (AR) knockout impacts uterine abnormalities and carcinogenesis in PTEN-deleted mice. PTEN knockout animals exhibited numerous uterine pathologies that were significantly reduced in combined heterozygous PTEN and AR knockout mice. Evidence suggested this effect may involve oestrogen receptor (ER) signalling, as reduced stromal ERa was noted in the uteri of PTEN knockouts compared to the double PTEN/AR deleted animals, suggesting crosstalk exists between AR and ERa in uterine tissue.
These data demonstrates the first in vivo evidence that androgen signalling may play an important role in uterine cancer development, and that anti-androgens might be novel therapies for the prevention and in early-stage uterine cancer.
Choi JP, Desai R, Zheng Y, Yao M, Dong Q, Watson G, Handelsman DJ, Simanainen U.
Endocr Relat Cancer. 2015 Oct;22(5):687-701.