Novel Cytochrome P45O1B1 as a Mammary Cancer Risk Factor.
Abstract
This work aims to elucidate whether cytochrome P45O iBI (CYP1B1) and the related P45O lAl (CYP1Al) are determinants or markers for breast cancer. Potential mechanisms include carcinogenic activation of polycyclic hydrocarbons (PAH) and of 17 Beta-estradiol to 4-catecholestrogens. Both processes may be modulated by organochiorine compounds via the Ah-receptor (PCB's), the estrogen receptor (ER), or Ca elevation (hexachlorocyclohexanes). We have established quantitative rtPCR methods to measure levels of CYP1Al and CYP1B1 mRNA in breast cells, and have generated affinity purified antibodies to measure CYP1B1 protein levels in microsomes (immunoblots) and tissue sections (immunocytochemistry). CYP1B1 expression has been established (mRNA and microsomal protein) in normal human breast epithelial cells, breast fibroblasts, and carcinoma cell lines. The Ah-receptor stimulant 2, 3, 7, 8 tetrachlorodibenzodioxin (TCDD) elevates CYP1B1 expression in epithelial and carcinoma cells, but not in fibroblasts. Unlike CYP1Al, induction of CYP1B1 by TCDD is not dependent on ER. A program for collection of breast tumors has been established and rtPCR has been used to detect CYP1B1 mRNA in these tumors. PAH metabolism in normal human breast cells is variable between individuals and is sensitive to culture conditions. The role of CYP1B1 in this variability is currently under investigation. CYP1B1 has been localized in ductal epithelia of terminal end buds in human and rat mammary gland, but is selectively expressed in stroma in subsequently cultured rat cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 28, 1995
- Accession Number
- ADA298701
Entities
People
- Colin R. Jefcoate
Organizations
- University of Wisconsin–Madison