The Weigel laboratory has had a long-standing interest in determining mechanisms of hormone response in breast cancer. Our work has identified transcriptional mechanisms that regulate the expression of estrogen receptor- alpha in breast carcinomas. Other areas of investigation have sought to identify genes that are related to hormone response and additional mechanisms of gene regulation that are responsive to estrogen. Current Projects Regulation of ER by AP2 . We identified the AP2? transcription factor as a key regulator of hormone response in breast cancer. We are now examining mechanisms of gene regulation that involve this transcription factor. Chromatin Effects Altering AP2 Activity. We have shown that epigenetic chromatin alterations can influence activity of AP2 at certain promoters. The mechanism appears to involve altered binding of AP2 mediated through chromatin structure. Studies to determine how chromatin structure alters AP2 activity are being pursued. Interaction of AP2 and p53. We demonstrated a direct interaction between AP2 factors and the p53 tumor suppressor. The interaction of p53 and AP2 has functional effects on these two factors that appear to alter hormone response in breast cancer and cell growth in other cancer types. We are investigating the details of this interaction and the functional effects on gene regulation and cell physiology.