Professor Satyabrata Nandi

Department of Molecular and Cellular Biology

Dr. Nandi's laboratory conducts research on breast cancer using in vivo and in vitro experimental approaches to determine the biological and molecular bases for susceptibility and resistance to breast carcinogenesis and for its prevention. By using the rat mammary carcinogenesis model system, the research focuses on elucidation of the mechanisms involved in determining the high susceptibility and high resistance of nulliparous and parous rats, respectively, to chemically induced breast carcinogenesis.

Breast cancer, like many other cancers, is a disease of aging. The Nandi lab's main goal is to devise hormonal prevention of breast cancer, beginning at a relatively early age, by mimicking the protective effect of pregnancy. It has been known for about thirty years that in women a first full-term pregnancy (FFTP) up to the age of thirty has a permanent effect on reducing the lifetime risk for developing breast cancer. Women undergoing FFTP after the age of 35 have the highest risk of developing breast cancer. The earlier the age at FFTP, the greater is the protection from breast cancer. This phenomena is, by far, the best normal, physiological, preventive measure against breast cancer.

Parity in rats and mice also results in refractoriness to chemical carcinogen induced breast carcinogenesis. Dr. Nandi's laboratory has made considerable progress in analyzing the biological basis for parity-induced refractoriness to N-methyl-N-nitrosourea (MNU) induced mammary carcinogenesis in rats. The research has recently been able to mimic the protective effect of pregnancy and succeeded in developing a short-term hormonal treatment procedure using estradiol, with or without progesterone, which prevents MNU induced mammary carcinogenesis in rats by over 80%. Such studies also suggest that the elevated blood levels of estrogens and progesterone during pregnancy are likely to be the major cause of parity-induced refractoriness to mammary cancer in rats. The ultimate goal of these studies is to generate an experimental paradigm that can be used to develop strategies for the prevention of human breast cancer without adverse effects on health or significant alterations in the quality of life. Thus, the main interest of Dr. Nandi's current research is to investigate the biological nature of parity-induced refractoriness and the susceptibility of nulliparous females to mammary carcinogenesis at the molecular level by expanding our ongoing studies using the rat experimental model. Little is known in terms of gene regulation of parity-induced refractoriness in the mammary gland. Therefore, Dr. Nandi's laboratory thoroughly investigates differential gene expression between mammary glands which are either susceptible (nulliparous) or refractory (parous or hormone-treated nulliparous). The rat model system is utilized since it best represents aspects of human breast cancer, and differential and DNA array display technology is used to identify differential gene activities between susceptible and refractory mammary glands.

At the molecular level, it is hypothesized that gene expression patterns are likely to be different between susceptible target cells and their differentiated counterparts in the mammary gland, and that as a consequence of pregnancy, there will be altered patterns of specific gene expression in the mammary glands of the refractory parous and estrogen- and progesterone-treated nulliparous females compared to the mammary glands of susceptible, young, untreated, nulliparous females.