Abstract 1466: Molecular insights of resistin associated proliferation by inducing hypercholesterolemia in breast cancer

Abstract

Abstract Introduction: Breast cancer is the most prevalent cancer in women impacting ~2.1 million women each year (WHO, 2019). It is the second leading cause of death after lung cancer in women. In spite of several therapeutic advances, further improvement in prognosis and survivability is still desired. According to numerous studies, Resistin, a proinflammatory cytokine, has a positive correlation with breast tumor progression. It plays multifaceted roles in diabetes, obesity, cardiovascular diseases as well as in several cancers. Despite several epidemiological studies showing an increase in serum resistin level in breast cancer patients, its relevance is not clearly understood. In the present study, we have focused on the role of resistin in breast cancer and emphasized on metabolic alterations occurring in this process. Methods: In vitro studies include long term colony formation and LDL estimation assays, immunoblotting, immunofluorescence . For in vivo studies, female Balb/C mice were used as isograft breast cancer model. Results: In vitro studies show that resistin facilitates progression of breast cancer through activation of JAK-STAT pathway. Downstream targets, c-Myc and cdc25A are also regulated via Resistin. Inhibition of JAK-STAT pathway abrogates resistin induced growth in breast cancer cells. Moreover, resistin also promotes cholesterol accumulation thereby inducing a hypercholesterolemic environment. In vivo studies indicate that with increase in tumor progression, resistin as well as LDL levels are also elevated in serum. Conclusions: In vitro as well as in vivo studies show that increase in serum resistin level is positively correlated with breast cancer progression and induction of hypercholesterolemia. Insights into resistin associated molecular events contributing to metabolic changes might facilitate progression of breast cancer. Targeting this pathway might contribute to a better therapeutic outcomes. Citation Format: Ankita Deb, Manoj Bhat. Molecular insights of resistin associated proliferation by inducing hypercholesterolemia in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1466.