Steroid Hormonal Independence of HER-2/ neu mRNA Expression in Four Human Ovarian Carcinoma Cell Lines

Abstract

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 × 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.