Pauline Suwandhi, MD
Research Fellow – Gerald J Friedman Diabetes Institute
Division of Endocrinology and Metabolism
Endocrine Research Laboratory, Mount Sinai Beth Israel,
New York, NY
Mentors Dr. Poretsky & Dr. Seto-Young
I have been a Friedman Research Fellow since July 1st 2010 under the tutelage of Friedman Research Mentors, Seto-Young, Ph.D. and Leonid Poretsky, M.D.
My research interest is to study the potential role of thiazolidinediones (TZDs, rosiglitazone and pioglitazone) in the treatment of breast cancer.
Breast cancer has been the most common cancer in female and second most common cause for cancer death among women in the US. Breast cancer is a hormone-dependent tumor and estrogen plays an important role in the development and progression of breast cancer. Clinical data suggesting high levels of circulating estrogen and aromatase activity are prevalent among breast cancer patients. Current data from clinical trials indicate that aromatase inhibitors (i.e. anastrozole, letrozole and exemestane) are equivalent or superior to tamoxifen as adjuvant treatment for primary breast cancer in the menopausal women.
TZDs, one of the current medications used for the type 2 diabetes treatment, are highly selective activating ligands for peroxisome proliferator-activated receptor-γ (PPAR-γ). PPAR-γ has been implicated as important regulators in many physiological functions, including lipid and glucose metabolism and cell differentiation. Our research data demonstrated that TZDs inhibit estrogen synthesis by interfering with androgen binding to aromatase and altering enzyme kinetic properties. TZDs act as un-competitive aromatase inhibitor, thus, we hypothesis that TZDs may play a role in treatment of breast cancer by inhibiting of estrogen synthesis and aromatase activity.
The project will attempt to explore TZDs’ potential role in tumor regression of human breast cancer in an animal model. First, we will transfect the aromatase gene to breast cancer cell line MCF-7. Then, the transfected aromatase cancer cell will be transplanted to ovariectomized mice to induce breast tumors. The mice will be divided into 3 groups, placebo, and treatment with rosiglitazone or pioglitazone. Treatment will be started after the tumors reach the volume of 300mm3. Breast tumor volume and serum estradiol and estrone levels will be measured every month. After 6 months, half of the mice in each group will be sacrificed and tumor weight and volume will be measured. The remaining mice will undergo observation on their survival.
The expected result of the project is that TZD will induce reduction of serum estrogen levels and breast tumor volume in mice and increase survival of mice with breast cancer. We are hopeful to be able to present an abstract in national meetings, such as the Annual Gerald J Friedman Fellows Symposium, Endocrinology Society and American Society of Clinical Oncology Annual Meeting.