Epithelin/Granulin Precursor Expression in Human Breast Carcinoma

Abstract

Abstract : Breast cancer is a major cause of morbidity and mortality in women worldwide. Breast tumors are initially estrogen-dependent but eventually become estrogen-independent and refractory to anti-estrogen therapy. Thus, it is very important to develop new insights into breast cancer. Our approach has been to analyze the cellular changes associated with highly tumorigenic properties. We have characterized a novel growth factor, PC-cell derived growth factor (PCDGF) (epithelin/granulin precursor) in human breast carcinoma cells. This application investigates the role of PCDGF in the proliferation of human breast cancer cells. In estrogen-receptor positive cells, PCDGF expression was stimulated in a dose and time-dependent fashion by estradiol and inhibited by tamoxifen. In estrogen-receptor negative cells, PCDGF was constitutively overexpressed. PCDGF acted as an autocrine growth factor both for ER(+) and ER(-) cells. Most importantly, inhibition of PCDGF expression by anti sense PCDGF cDNA transfection in ER(-) breast carcinoma led to a 90% inhibition of tumor incidence and size. These characteristics make PCDGF an important factor involved in the tumorigenicity of breast carcinoma. Future goals are to further investigate PCDGF role on the proliferation of breast cancer cells and examine PCDGF expression in human breast cancer biopsies at different stages of the disease.