Abstract 1818: Coregulation of progesterone receptor and O-GlcNAc in breast cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-07, Vol.76 (14_Supplement), p.1818-1818
• Main Authors: Trinca, Gloria, Goodman, Merit, Workman, Lauren, Carroll, Jason, D’Santos, Clive, Slawson, Chad, Hagan, Christy R.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2016-1818

Progesterone receptor (PR) activity is highly regulated by post-translational modifications. Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) analysis identified O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) as a PR-interacting protein. OGT catalyzes the addition of N-acetylglucosamine sugar moieties to serine/threonine residues in order to coordinate several cellular processes—including transcription, metabolism, and cell fate. Further investigation revealed that PR is O-GlcNAcylated, and enhanced OGT activity subsequently decreases PR protein stability. Interestingly, PR-expressing breast cancer cells display lower OGT levels in comparison to PR-null counterparts, suggesting that PR may govern its own O-GlcNAcylation or that of other key regulatory proteins. Our lab previously identified a phosphorylation site at Ser-81 in PR that potentiates the expression of PR proliferative target genes. Phosphorylation and O-GlcNAcylation are known to compete for the same residue substrates; and our preliminary data suggests that PR O-GlcNAcylation may also alter its transcriptional activity for a subset of target genes. While the role of PR in breast cancer progression is well characterized, the overall effect of protein O-GlcNAcylation within these tumors remains highly controversial. Collectively, our data supports a potential regulatory mechanism wherein OGT serves to restrain PR function in early PR+ tumors; whereas those that have lost PR expression may exhibit the elevated pro-tumorigenic OGT activity previously associated with more advanced breast cancers. As such, the continued study of O-GlcNAcylation with respect to PR stability, phosphorylation, and transcriptional activity may lead to a clearer understanding of these effectors and their contribution to breast cancer progression. Citation Format: Gloria Trinca, Merit Goodman, Lauren Workman, Jason Carroll, Clive D’Santos, Chad Slawson, Christy R. Hagan. Coregulation of progesterone receptor and O-GlcNAc in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1818.