Breast cancer is likely the result of the interaction of several factors, all of which must be present for cancer to be manifested. The understanding of breast cancer requires a further knowledge of the factors regulating the susceptibility of the organ to carcinogenesis, which requires the demonstration that transformation from normal to neoplastic takes place under the influence of a given etiological agent, which could be a chemical carcinogen. Therefore this proposal intends to answer the following questions: (i) Is the human breast epithelium susceptible to neoplastic transformation by the chemical carcinogens that are known to cause cancer in experimental animals? (ii) if the human mammary gland is susceptible to neoplastic transformation in vitro, what are the biological parameters that regulate this susceptibility? and (iii) is the susceptibility to tranformation determined by the patient's reproductive history, a factor known to affect the development of breast cancer in vivo? These studies will be carried out using primary cultures or early passages of human breast epithelium from tissue obtained at surgery or from recent post-mortem specimens from three groups of women: (a) parous, premenopausal women with an early full term pregnancy (before age 24 years), known to be at low risk for development of breast cancer, (b) nulliparous, premenopausal women age-matched with group a, known to have four times higher risk than the former of developing breast carcinoma and (c) young nulliparous women between ages 12-14 years in whom the mammary gland is relatively undifferentiated and therefore likely to be more susceptible to carcinogenesis. The cells will be treated with two chemical carcinogens, (DMBA and MNU) which have different metabolic pathways of activation but the same effect in inducing mammary carcinoma in experimental animals. Neoplastic transformation will be measured by the expression of phenotypic changes and by tumorigenicity in heterologous hosts.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038921-02
Application #
3177386
Study Section
Pathology B Study Section (PTHB)
Project Start
1984-12-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Barbara Ann Karmanos Cancer Institute
Department
Type
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48201
Calaf, G; Russo, J; Tait, L et al. (2000) Morphological phenotypes in neoplastic progression of human breast epithelial cells. J Submicrosc Cytol Pathol 32:83-96
Lah, T T; Calaf, G; Kalman, E et al. (1996) Cathepsins D, B, and L in transformed human breast epithelial cells. Breast Cancer Res Treat 39:221-33
Russo, J; Russo, I H (1995) The etiopathogenesis of breast cancer prevention. Cancer Lett 90:81-9
Lah, T T; Calaf, G; Kalman, E et al. (1995) Cathepsins D, B and L in breast carcinoma and in transformed human breast epithelial cells (HBEC). Biol Chem Hoppe Seyler 376:357-63
Russo, J; Russo, I H (1995) Hormonally induced differentiation: a novel approach to breast cancer prevention. J Cell Biochem Suppl 22:58-64
Mello, M L; Lin, T Y; Russo, J (1994) Scanning microphotometry image analysis of Ha-ras-transformed human breast epithelial cells. Anal Cell Pathol 7:301-19
Calaf, G; Tahin, Q; Alvarado, M E et al. (1994) Hormone receptors and cathepsin D levels in human breast epithelial cells transformed by chemical carcinogens and c-Ha-ras transfection. Breast Cancer Res Treat 29:169-77
Ho, T Y; Russo, J; Russo, I H (1994) Polypeptide pattern of human breast epithelial cells following human chorionic gonadotropin (hCG) treatment. Electrophoresis 15:746-50
Russo, J; Russo, I H (1994) Toward a physiological approach to breast cancer prevention. Cancer Epidemiol Biomarkers Prev 3:353-64
Russo, J; Romero, A L; Russo, I H (1994) Architectural pattern of the normal and cancerous breast under the influence of parity. Cancer Epidemiol Biomarkers Prev 3:219-24

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