Accession Number : ADA406230


Title :   Effects of Environmental Estrogens on Apoptosis in Normal and Cancerous Breast Epithelial Cells


Descriptive Note : Final rept. 1 May 1997-28 Feb 2001


Corporate Author : TULANE UNIV MEDICAL CENTER NEW ORLEANS LA


Personal Author(s) : Burow, Matthew E


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a406230.pdf


Report Date : Mar 2001


Pagination or Media Count : 111


Abstract : Estrogens and environmental estrogens were shown to suppress apoptosis in MCF-7 cells and increase expression of Bcl- 2. These same compounds were unable to suppress apoptosis of MDA-MB-231 cells suggesting an ER-dependent mechanism of action. Phytoestrogens represent another category of environmental estrogens some of which our results demonstrate possess anti-estrogenic activity and induce apoptosis in MCF-7 cells. To investigate the role of Bcl-2 in TNF resistance by estrogens a Bcl-2 expression vector was transfected into MCF-7 cells and stable clones were established. These clones express higher levels of Bcl-2 as compared to vector transfected MCF-7N/Neo cells. The BCL-2 overexpressing cells exhibited a greater resistance to apoptosis as compared to MCF-7N/Neo cells. However suppression of ER function by the anti-estrogen 101182,780 blocked the ability of Bcl-2 to inhibit apoptosis suggesting that Bcl-2 was necessary but not sufficient for suppression of apoptosis by estrogen signaling. Subsequent experiments provided evidence that ER suppression of apoptosis was dependent upon both Bcl-2 expression and regulation of signaling by the mitogen-activated protein kinase cascades. We have identified environmental compounds that function to regulate the apoptotic response of breast carcinoma cells through regulation of MAPK signaling and Bcl-2 expression.


Descriptors :   *APOPTOSIS , *BREAST CANCER , *ESTROGENS , EPITHELIUM , MAMMARY GLANDS , MITOSIS , PHOSPHOPROTEINS , TOLERANCES(PHYSIOLOGY)


Subject Categories : Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE