Christy R. Hagan, PhD

Professional Background

My lab studies the role of hormones in breast cancer. In particular, we are interested in how the ovarian steroid hormone, progesterone, works together with its receptor, the progesterone receptor (PR), to influence breast cancer biology. Mounting clinical data continues to implicate progesterone and PR in breast cancer progression. Upon diagnosis, nearly 70% of breast cancers express PR and the estrogen receptor (ER). In contrast, only 7-10% of normal luminal epithelial cells express ER and PR. ER action in breast cancer has been well studied and as a result, ER has proven to be an excellent target for current endocrine-based therapies. However, despite convincing clinical trial data implicating progesterone in the development of invasive breast cancer, the role of progesterone/PR in breast cancer has been largely understudied. Despite maintaining receptor (ER/PR) expression, many breast cancer patients eventually progress to hormone-independence, failing current (largely ER/estrogen based) endocrine therapies. Therefore, ER-independent functions of PR are of great clinical interest.

• BA, Biochemistry, Colorado College
• PhD, Cancer Biology, University of Chicago
• Post Doctoral Fellowship, Cancer Biology, Northwestern University, Chicago, IL
• Post Doctoral Fellowship, Cancer Biology, University of Minnesota, Minneapolis, MN

Research

Overview

Our current work is focused on how PR may promote breast tumor progression through evasion of immune surveillance. Interferon-activation is a key step in immune surveillance and destruction of nascent tumors. We recently described how interferon-stimulated genes, an end product of interferon signaling, are transcriptionally repressed by PR through modulation of STAT1 and STAT2. This represents a novel subset of genes not previously known to be regulated by PR. Moreover, PR-dependent attenuation of interferon signaling suggests a mechanism through which PR may aid early breast cancer lesions in escaping immune surveillance. As such, we have shown that PR promotes immunosuppressive changes in the immune microenvironment of the mammary gland. We've shown that these immunosuppressive changes lead to the development of mammary gland tumors. These data have significant implications for the use of progesterone-containing hormone replacement therapy in post-menopausal women, as well as underscore the importance of studying anti-progestins (synthetic progesterone) as novel chemo-preventative agents for breast cancer. Moreover, modulating PR action in breast tumors may make these tumors more susceptible to treatment with new immunotherapy agents, such as checkpoint inhibitors.

• Walter, K., R, Goodman, M., L, Singhal, H, Hall, J., A, Li , T, Holloran, S., M, Trinca, G., M, Gibson, K., A, Jin, V., X, Greene, G., L, Hagan, C., R. 2017. Interferon-Stimulated Genes Are Transcriptionally Repressed by PR in Breast Cancer.. Molecular cancer research : MCR, 15 (10), 1331-1340
• Hagan, C., R, Lange, C., A. 2014. Molecular determinants of context-dependent progesterone receptor action in breast cancer.. BMC medicine, 12, 32
• Trinca, G., M, Goodman, M., L, Papachristou, E., K, D'Santos, C., S, Chalise, P, Madan, R, Slawson, C, Hagan, C., R. 2018. O-GlcNAc-Dependent Regulation of Progesterone Receptor Function in Breast Cancer.. Hormones & cancer, 9 (1), 12-21
• Trinca, G., M, Hagan, C., R. 2018. O-GlcNAcylation in women's cancers: breast, endometrial and ovarian.. Journal of bioenergetics and biomembranes, 50 (3), 199-204
• Goodman, M., L, Trinca, G., M, Walter, K., R, Papachristou, E., K, D'Santos, C., S, Li , T, Liu, Q, Lai, Z, Chalise, P, Madan, R, Fan, F, Markiewicz, M., A, Jin, V., X, Carroll, J., S, Hagan, C., R. 2019. Progesterone Receptor Attenuates STAT1-Mediated IFN Signaling in Breast Cancer.. Journal of immunology (Baltimore, Md. : 1950), 202 (10), 3076-3086
• Walter, K., R, Balko, J., M, Hagan, C., R. 2020. Progesterone receptor promotes degradation of STAT2 to inhibit the interferon response in breast cancer.. Oncoimmunology, 9 (1), 1758547
• Holloran, S., M, Nosirov, B, Walter, K., R, Trinca, G., M, Lai, Z, Jin, V., X, Hagan, C., R. 2020. Reciprocal fine-tuning of progesterone and prolactin-regulated gene expression in breast cancer cells.. Molecular and cellular endocrinology, 511, 110859