Hormone receptors and cathepsin D levels in human breast epithelial cells transformed by chemical carcinogens and c-Ha-ras transfection.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Calaf
G
G
Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111.
Tahin
Q
Q
Alvarado
M E
ME
Estrada
S
S
Cox
T
T
Russo
J
J
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001940:Breast / Q000187:drug effects / Q000378:metabolism*; D001943:Breast Neoplasms / Q000473:pathology*; D002402:Cathepsin D / Q000378:metabolism*; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002633:Chemotaxis; D002999:Clone Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D011905:Genes, ras; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014162:Transfection; D014183:Transplantation, Heterologous
D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D066246:ErbB Receptors; D002402:Cathepsin D