SOTO LABORATORY

1. Control of Cell Proliferation: The purpose of my research is to understand the mechanisms that regulate cell proliferation in both normal and cancer cells. Sex hormones are known to regulate cell proliferation on their target organs. Two models are being studied: human breast cells, which are responsive to estrogens, and human prostate cells which are sensitive to androgens. This research revealed that the proliferation of these hormone-sensitive cells is controlled negatively by specific plasma-borne inhibitors (estrocolyone-I for estrogen-sensitive cells; androcolyone-I for androgen-sensitive cells). Sex hormones induce cell proliferation by neutralizing the effect of the plasma-borne inhibitors.

Sex hormones also inhibit the proliferation of their target cells (shutoff effect). It is postulated that hormone-sensitive tumors arise when the shutoff mechanism is altered. We developed androgen-receptor stable transfectants that express the androgen-induced proliferative shutoff, and identified candidate genes that mediate the sex steroid-induced proliferative shutoff by means of subtracted libraries. The role of these candidates is being studied (antisense oligonucleotides, expression vectors, microinjection). We propose that cancer arises when one or both of the above mentioned mechanisms is (are) damaged. We expect that these transfected cell lines, shutoff gene candidates, and the recently identified estrocolyone-I would shed light on the role of sex steroids and their receptors on the control of cell proliferation.

2. Environmental Reproductive Toxicology: Environmental pollutants are disrupting the reproductive success of wildlife and probably of humans. My research objective is to understand their mechanism of action. I am exploring the hypothesis that in utero exposure to minute quantities of xenoestrogens affect irreversibly the development of the female genital tract. Transplacental dosimetry and pharmacokinetics are studied using radiolabelled bisphenol-A. Metabolites are identified by HPLC separation of labeled products. Effects to be measured comprise several hierarchical levels of organization, from molecular markers, such as the expression of estrogen receptor mRNA during development of the genital tract by RT-PCR, to physiological parameters such as fertility of the exposed offspring at adulthood.