Comparative cistromic analysis reveals a shift in tamoxifen-associated endometrial tumor ERα binding toward sites less frequently shared by progesterone receptors

Non-user ERα binding in Ishikawa endometrial adenocarcinoma tumors is more similar to the PR cistrome than tamoxifen-user tumors, indicating a tamoxifen-linked shift in ERα binding patterns.

• Why it matters: Tamoxifen increases endometrial cancer risk, but how long-term exposure alters ERα/PR binding interplay in endometrial tumors is unknown.
• What they did: The study compared ERα cistromes from tumors of tamoxifen users versus non-users with Ishikawa ERα and PR cistromes to assess shared binding sites and motif enrichment.
• The result: Shared ERα–PR sites in non-users are enriched in AP-1 and SOX motifs (not EREs) and associate with inflammatory genes like MYC, while tamoxifen exposure shifts ERα toward PR-independent ERE-enriched regions linked to early estrogen response genes including NRIP1.