STEROID HORMONAL INDEPENDENCE OF HER-2/NEU MESSENGER-RNA EXPRESSION IN 4 HUMAN OVARIAN-CARCINOMA CELL-LINES

Overexpression of HER-2/neu, a 185-kDa tyrosine kinase growth factor receptor, in human ovarian cancers has been correlated with a poor prognosis for survival of the disease. Previous studies have demonstrated that dexamethasone (Dex) induces a dose-dependent increase in HER-2/neu mRNA levels in the ovarian cancer cell line SK-OV-3 by stabilizing the HER-2/neu message. We extended these studies to test whether estrogen (Es), progesterone (Pr), and Dex were capable of regulating HER-2/neu mRNA levels in the human ovarian cancer cell lines NIH:OVCAR-3, SW 626, OVCA 433, and Caov-3. Southern blotting demonstrated that all four cell lines contained a single copy of the 12.5-kb HER-2/neu gene. Blotting techniques demonstrated low to barely detectable levels of HER-2/neu mRNA and protein in these cell lines. To determine whether steroids regulated HER-2/neu expression, all four ovarian cancer cell lines were cultured in the presence of 1 x 10(-7) M Es, Pr, or Dex and Northern blotting was completed. Unlike SK-OV-3 cells, the cell lines tested did not respond to the steroid treatments with alterations in their HER-2/neu mRNA levels. In conclusion, neither Es, Pr, nor Dex regulates HER-2/neu mRNA levels in NIH:OVCAR-3, SW 626, OVCA 433, and Caov-3 ovarian cancer cells. Future therapeutic manipulations of HER-2/neu should not involve hormonal intervention. (C) 1994 Academic Press, Inc.