Role of human growth hormone-regulated HOXA1 in mammary gland neoplastic progression

Abstract

Abstract Name: Zhang Xin Degree: Ph.D. Dept: Medicine Thesis title: Role of human growth hormone-regulated HOXA1 in mammary gland neoplastic progression Previous microarray studies showed that autocrine human growth hormone (hGH) production by human mammary carcinoma cells (MCF-7) upregulated the homeobox gene, HOXA1. The present work investigated the role of autocrine GH regulated HOXA1 in MCF-7 and MCF-10A (immortalized but not transformed) cell lines in vitro, and in severe combined immunodeficient (SCID) mice in vivo. Forced expression of HOXA1 in stably transfected MCF-7 cells resulted in increased total cell number primarily by the promotion of cell survival mediated by the upregulation of Bcl-2, and enhancement of anchorage independent proliferation and colony formation in soft agar. Furthermore, forced expression of HOXA1 was sufficient to result in the oncogenic transformation of MCF-10A with aggressive in vivo tumor formation in SCID mice. Finally, HOXA1 expression was found to be significantly increased in MCF-7 cells at full confluence and this increment was demonstrated to be directed by E-cadherin signaling through Rac1.