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Calaf G , Tahin Q , Alvarado ME , Estrada S , Cox T , Russo J
Hormone Receptors and Cathepsin-D Levels in Human Breast Epithelial-Cells Transformed by Chemical Carcinogens and C-Ha- Ras Transfection
Breast Cancer Research and Treatment. 1994 ;29(2) :169-177
PMID: ISI:A1994NB59300003   
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The objective of this work was to determine whether transformation of the human breast epithelial cell line MCF-10F by the chemical carcinogens 7,12-dimethylbenz(a)anthracene (DMBA) or benzo(a)pyrene (BP), or c-Ha-ras oncogene transfection, influence the expression of epidermal growth factor receptor (EGFR), estrogen (ER) or progesterone (PR) receptors, and the content of cathepsin-D (Cath.D). MCF-10F control cells did not express any of the phenotypes of neoplastic transformation, whereas carcinogen-treated cells and clones derived from the latter formed colonies in agar- methocel, and exhibited increased chemotaxis and chemoinvasion. Clone BP-1E was also tumorigenic in SCID mice. The BP1 cell line transfected with mutated c-Ha-ras oncogene, named BP1- Tras, became more aggressive after transfection and decreased the latency time to tumorigenesis. Radioligand binding and immunocytochemical reactions were utilized for determining the receptors and Cath.D content of control and carcinogen-treated cells and their derived clones. MCF-10F cells contained 37 fmol/mg of protein of EGFR, ER and PR were undetectable, and Cath.D content was 70 fmol/mg protein. EGFR content was significantly higher in D3-1 and BP1-E cell lines vs the control MCF-10F and the other DMBA and BP clones, correlating positively with the emergence of the transformation phenotype. Whereas EGFR levels were not significantly different in BP1- Tras cells when compared with BP1-E, the former were more tumorigenic in SCID mice, an observation suggesting an alternative pathway in these cells in the formation of tumors. PR, ER, and Cath.D content was not modified by either carcinogen treatment or ras transfection in most of the clones and subclones, except clone BP2 that has a significant increase in ER content, and was not associated with any of the neoplastic phenotypes. These data allowed us to conclude that the level of EGFR is associated with the expression of carcinogen-induced transformation phenotypes whereas ER, PR, and Cath.D did not seem to be modified during the process of chemically induced or c-Ha-ras enhanced transformation of MCF- 10F cells.