Professor Emeritus of Cell and Developmental Biology
Our laboratory performs research on breast cancer. We are using in vivo and in vitro experimental approaches to determine the biological and molecular bases for susceptibility and resistance to breast carcinogenesis as well as for the prevention of breast cancer. By using the rat mammary carcinogenesis model system, we are currently focusing on studies to elucidate the mechanisms involved in determining the high susceptibility and high resistance of nulliparous and parous rats, respectively, to chemical carcinogen induced breast carcinogenesis.
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. 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. During the last several years, we have made considerable progress in analyzing the biological basis for parity-induced refractoriness to N-methyl-N-nitrosourea (MNU) induced mammary carcinogenesis in rats. We have recently been able to mimic the protective effect of pregnancy and succeeded in developing a short-term hormonal treatment procedure using natural steroids which prevents MNU induced mammary carcinogenesis in rats. These current 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 our 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, we have undertaken a thorough analysis of the above projects by investigating differential gene expression between mammary glands which are either susceptible (nulliparous) or refractory (parous or hormone treated nulliparous). We want to focus on the rat model system because it best represents aspects of human breast cancer. We willutilize differential as well as the DNA array display technology to identify differential gene activities between susceptible and refractory mammary glands.
At the molecular level, we hypothesize that gene expression patterns are likely to be different between susceptible target cells and their differentiated counterparts in the mammary gland. We further hypothesize that as a consequence of pregnancy, there will be altered patterns of specific gene expression in the mammary glands of refractory parous and estrogen and progesterone treated nulliparous females compared to the mammary glands of susceptible, young, untreated, nulliparous females.
Short-term exposure to pregnancy levels of estrogen prevents mammary carcinogenesis. [L.Rajkumar, R.C. Guzman, J. Yang, G. Thordarson, F. Talamantes and S. Nandi. (2001) Proc. Nat. Acad. Sci. USA 98:11755-11759]
Growth and characterization of N-methyl-N-nitrosourea-induced mammary tumors in intact and ovariectomized rats. [G. Thordarson, A.V. Lee, M. McCarty, K. VanHorn, O. Chu, Y-C Chou, J. Yang, R.C. Guzman, S. Nandi, and F. Talamantes. (2001) Carcinogenesis 22:2039-2047]
Expression of MAT1/PEA-15mRNa isoforms during physiological and neoplastic changes in the mouse mammary gland. [T. Tsukamoto, J. Yoo, S.-I. Hwang, R. C. Guzman, Y. Hirokawa, Y.-C. Chou, S. Olatunde, T. Huang, T. K. Bera, J. Yang, and S. Nandi (2000) Cancer Letters 149, 105-113]
Hormonal prevention of breast cancer: Mimicking the protective effect of pregnancy. [R. Guzman, J. Yang, L. Rajkumar, G. Thordarson, X. Chen, and S. Nandi (1999) Proc. Natl. Acad. Sci. USA 96, 2520-2525]
Induction of mammary carcinomas by N-methyl-N-nitrosourea in ovariectomized rats treated with epidermal growth factor. [Y.-C. Chou, R. Guzman, S. Swanson, J. Yang, V. Wu, and S. Nandi (1999) Carcinogenesis 20, 677-684]
Protective effects of pregnancy and lactation against N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats. [J. Yang, K. Yoshizawa, S. Nandi, and A. Tsubura (1999) Carcinogenesis 20, 623-628]
Refractoriness to mammary tumorigenesis in parous rats: is it caused by persistent changes in the hormonal environment or permanent biochemical alterations in the mammary epithelia. [G. Thordarson, E. Jin, R. Guzman, S. Swanson, S. Nandi, and F. Talamantes (1995) Carcinogenesis 16, 2847-2854]
Refractoriness to mammary carcinogenesis in the parous mouse is reversible by hormonal stimulation induced by pituitary isografts. [S. Swanson, R. Guzman, G. Collins, P. Tafoya, G. Thordarson, F. Talamantes, and S. Nandi. (1995) Cancer Letters 90, 171-181]
Hormones and Mammary Carcinogenesis in Mice, Rats, and Humans: A Unifying Hypothesis. [S. Nandi, R. Guzman, and J. Yang (1995) Proc. Natl. Acad. Sci. USA 92, 3650-3657]
Last Updated 2003-09-02