Abstract 607: Loss of pigment epithelium derived-factor (PEDF) is associated with breast cancer progression and antihormone drug resistance

Abstract

Abstract Despite the benefits of antihormones in treating estrogen receptor (ER)-positive breast cancer, many tumors develop resistance. Pigment epithelium-derived factor (PEDF) is an endogenous antiangiogenic protein that is showing promise as a potential anticancer agent. PEDF is considered a potential tumor suppressor because its expression is very high in normal tissues but is loss or reduced in various types of malignancies. Previously, it was reported that PEDF expression was signficantly reduced in human breast cancer and that a lack of PEDF expression was a potent factor for the enhancement of tumor growth and angiogenesis. At present however, there are no studies which have examined whether PEDF plays a role in antihormone resistance. In this study, we have characterized the role of PEDF in breast cancer progression and assessed whether PEDF, through a possible interaction with the ER, plays a role in antihormone drug resistance. We found that PEDF expression was dramatically reduced in antihormone-resistant breast cancer cells compared to antihormone-sensitive cells and that reexpression of PEDF in these cells resensitized them to antiestrogens. In addition, we found that treatment of antihormone resistant breast cancer cells with recombinant PEDF significantly reduced the growth of these cells by inducing apoptosis and it reduced the ability of these cells to migrate and invade through an artificial basement membrane. Interestingly, we also found that PEDF expression was dramatically reduced in ER-negative versus ER-positive breast cancer cells; however, there was no significant correlation between PEDF expression and ER in our antihormone resistant cells which continued to expressed high levels of ER despite their PEDF-negative status. Overall, these observations support the hypothesis that a loss of PEDF expression plays an important role in antihormone resistance in breast cancer and they suggest that the presence of PEDF might be an important indicator of antihormonal responsiveness. This work was supported by the NIH Career Development Grant K01CA120051-01A2, the American Cancer Society Grant IRG-92-027-14; and the Hollenbach Family Fund. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 607.