• The Breast Cancer and the Environment Research Center
  • Project 1
  • Project 1 Publications
  • External Advisory Board
• Genomic Basis of Reproductive History in Breast Cancer
• Breast Cancer Therapy by Differentiation Gene Activation
• Estrogens and Breast Cancer
• Biomarkers of Exposure
• Biomarkers of Breast Cancer Prevention
• Epigenetics Control of Estrogen Induced Cell Transformation
• Prevention Trial in the use of r-hCG in Women of High Risk of Developing Breast Cancer
• Circadian Rhythm and Mammary Gland Development
• Fox Chase Cancer Center Breast Cancer Tissue Resources
• Characterization and Validation of Genomic Expression Signature of Pregnancy

The Breast Cancer and the Environment Research Center (BCERC):
Collaborative Project 1

We have hypothesized that exposure to estrogenically-active chemicals alone, or in combination with eachother, during early critical periods of development will alter predisposition for breast cancer. Our goal is to investigate the potential ability of environmental chemicals that are known endocrine disruptors to alter morphology and genomic/proteomic expressions that can alter mammary gland differentiation and therefore create a predisposition for breast cancer. To reach this goal, we are studying three compounds:

• Bisphenol A (BPA) – A monomer used to manufacture polycarbonate plastic, the resin used for most food and beverage cans, dental sealants and more.
• Butyl Benzyl Phthalate (BBP) – A plasticizer used in PVC, vinyl foams, traffic cones, food conveyor belts, artificial leather, plastic foams. It can also be found in some cosmetics.
• 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD) – A highly toxic dioxin produced mainly by combustion, including incineration of waste and burning fuels. It is also found in some herbicides.

These compounds were used separately to treat the rats at two early periods of development: Prenatal (while the rats are developing intrauterus, the compound is received through the placenta)and Prepubertal (during the lactation, the compound is received through the milk of the mother). The study of the female offspring was performed when they reached 21, 35, 50 or 100 days old (Figure 1: Click to see).

Figure 1: Time line of rat’s life. The gestation of the rat lasts around 21 days (prenatal). 0 is the day of birth, and at 21 days of age, the rats are weaned. The treatments were realized during the prenatal or prepubertal stage of life and the mammary glands were collected at 21, 35, 50 and 100 days.

Julia S. Pereira at FCCC

After the mammary glands of the animals were collected, they were used for morphological analysis using whole mount preparations and cell proliferation studies.  In addition, RNA was extreacted from the mammary glands, which was used for gene expression analysis through microarray analysis and real time RT-PCR. Biostatistics and Bioinformatics analysis have been done with the microarray results to determine gene expression profiles of exposure, as well to predict or explain changes in the development or cancer susceptibility (Figure 2: Click to see).

Figure 2: Design of the experiments realized for each treatment.

Figure 3: Interactive relationship among the UA and FCCC.

This project requires an interaction between the animal studies performed at the University of Alabama at Birmingham (UA) and the genomic studies performed at the Fox Chase Cancer Center (FCCC).  At UA the animals are treated according to the protocol described in Figure 6 and the mammary glands are collected and shipped to the FCCC, where the morphological, cell kinetics and genomic studies are performed. At UA, the proteomics studies are performed. (Figure 2). The informatics cores of the FCCC and the UA are extremely important for the data analysis and interpretation for the genomic and proteomic data respectively (Figure 3).

Main Publications Generated from this Project