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Faculty Profile

Carol A. Sartorius, Ph.D. Assistant Professor of Medicine

Estrogen Receptors (ER) and progesterone receptors (PR) are clinical markers that predict breast cancer responsiveness to endocrine therapies. Additionally, PRs alone are independent markers of good prognosis. ER and PR are present in the same cells and cross-talk between estrogen and progesterone signaling is well known. PRs exist as two forms called PR-A and PR-B. Normal cells contain equal amounts of A and B. However, the A:B ratio is often skewed in breast cancers: some tumors have B>A and some A>B. Recent studies have shown that the response to treatment is different in these two groups. We have established an in vivo tumor model in which human breast tumors are grown in a mouse host that contain: no PR, only PR-A, only PR-B, or both PR-A and PR-B. Using this model, we have shown that tumors have different growth properties depending on the PR content. We are now using this model to look at both i) growth properties and ii) gene expression profiles in animals treated with different progestins. We have chosen to look at the natural hormone progesterone and a synthetic progestin MPA (Depo-Provera). This progestin is commonly used clinically for such treatments as hormone replacement therapy, birth control, and cancer therapies. In addition to progestins we will look at treatment of established tumors with agents used for endocrine therapies: these include antiestrogens (Tamoxifen and Faslodex) and Aromatase inhibitors (for example Letrozole). Our ongoing and future experiments will define how PR content of ER positive tumors affects tumor growth and gene expression in response to routinely used progestins, and in response to endocrine treatments.

Selected Publications

  • Harrell JC, Dye WW, Allred DC, Jedlicka P, Spoelstra NS, Sartorius CA, Horwitz KB. Estrogen receptor positive breast cancer metastasis: altered hormonal sensitivity and tumor aggressiveness in lymphatic vessels and lymph nodes. Cancer Res. 2006 Sep 15;66(18):9308-15 PUBMED

  • Tung L, Abdel-Hafiz H, Shen T, Harvell DM, Nitao LK, Richer JK, Sartorius CA, Takimoto GS, Horwitz KB. Progesterone receptors (PR)-B and -A regulate transcription by different mechanisms: AF-3 exerts regulatory control over coactivator binding to PR-B. Mol Endocrinol. 2006 Nov;20(11):2656-70. PUBMED 

  • Sartorius CA, Harvell DM, Shen T, Horwitz KB. Progestins initiate a luminal to myoepithelial switch in estrogen-dependent human breast tumors without altering growth. Cancer Res. 2005 Nov 1;65(21):9779-88. PUBMED  

  • Harvell DM, Richer JK, Allred DC, Sartorius CA, Horwitz KB. Estradiol regulates different genes in human breast tumor xenografts compared with the identical cells in culture. Endocrinology. 2006 Feb;147(2):700-13. PUBMED

  • Jacobsen BM, Richer JK, Sartorius CA, Horwitz KB. Expression profiling of human breast cancers and gene regulation by progesterone receptors. J Mammary Gland Biol Neoplasia. 2003 Jul;8(3):257-68. PUBMED