The Hairy and Enhancer of Split homologue-1 (HES-1) mediates the proliferative effect of 17beta-estradiol on breast cancer cell lines.
The mechanism behind hormone dependent growth of breast cancer is presently not well understood. We show that the HES-1 protein level in the breast cancer cell lines T47D and MCF-7 is down regulated by 17beta-estradiol treatment. This regulation could be reversed by addition of the anti-estrogens 4OH tamoxifen, raloxifen and Imperial Chemical Industries (ICI) 182,780. In T47D cells with inducible exogenous HES-1 expression, induced expression of HES-1 protein prevented the proliferative effect of 17beta-estradiol and subsequent up regulation of proliferating cell nuclear antigen (PCNA). An inverse correlation between the HES-1 and PCNA protein levels respectively was found in colon cancer cell lines. These findings point to a potential role of HES-1 as a tumor suppressor in epithelial cells, and as a mediator of 17beta-estradiols proliferative effect on breast cancer cells.
Ström
A
A
Center for Biotechnology, Karolinska Institute, Huddinge, Sweden.
Arai
N
N
Leers
J
J
Gustafsson
J A
JA
D051792:Basic Helix-Loop-Helix Proteins; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D000072056:Transcription Factor HES-1; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D004958:Estradiol; D004965:Estrogen Antagonists; D018398:Homeodomain Proteins; D018809:Proliferating Cell Nuclear Antigen; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human