| Estrogen plays a crucial role in the development and evolution of human breast cancer. But the mechanism of action of estrogen as a carcinogen in human breast cancer is still unclear. While one possible mechanism may include the formation of reactive oxygen species (ROS) and/or a receptor-mediated pathway, other reports suggest that estradiol (E2), the most active member of the estrogen family of female sex hormone, could act as an antioxidant that could enhance anti-apoptotic activity.; Tamoxifen (TAM) is well known as an adjuvant treatment in estrogen-dependent breast cancer. The main mechanism of action of TAM is believed to be as the estrogen-receptor (ER) agonist, which would inhibit estrogen's function. And there exist other mechanisms of TAM as anti-tumor drug, such as modulation of signaling proteins, oxidative stress, etc.; Our experiments are mainly focused on the characterization and quantification of the genes related to ER function, and others related to the antioxidant and anti-apoptotic functions. We have used human ER-positive (ZR-75-1) and ER-negative (MDA-MB-231) breast cancer cell lines as in vitro models to study alterations in the expressions of the following classes of genes in response to TAM and E2 treatments: (a) protooncogenes, (b) Tumor suppress genes, (c) Estrogen related protein genes, and (d) Antioxidant enzyme genes. We have quantified gene expressions using real-time PCR. In this manner, we have attempted to elucidate the antioxidant and antiapoptotic roles of E2 and TAM. The findings that we present here serve to enlarge our vision in understanding the TAM and estradiol networks and their interactions. |
