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Modulation of estrogen receptor and epidermal growth factor receptor mRNAs by phorbol ester in MCF 7 breast cancer
C S Lee1, M Koga, R L Sutherland
1Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, N.S.W., Australia.
Abstract:
Previous studies have demonstrated an inverse relationship between estrogen receptor (ER) and epidermal growth factor receptor (EGF-R) gene expression in human breast cancer cells. This relationship was further investigated in MCF 7 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). Exposure to 10 nM TPA resulted in a time-dependent increase in EGF-R mRNA, first apparent at 3 h and maximal between 9 and 24 h. There was a concomitant fall in ER mRNA with a maximum decline to 15-20% of control between 12 and 24 h. Although EGF-R mRNA levels declined between 24 and 72 h, both EGF-R mRNA and EGF-R binding remained above control levels and this was accompanied by a sustained depression of ER mRNA. These data support the view that ER and EGR-R gene expression is inversely regulated in human breast cancer and describe for the first time an inhibitory effect of a phorbol ester on steroid hormone receptor gene expression.
Insights
This study shows that phorbol ester treatment inversely affects estrogen receptor (ER) and epidermal growth factor receptor (EGF-R) gene expression in breast cancer cells. Phorbol ester increases EGF-R while decreasing ER gene expression.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Estrogen receptor (ER) and epidermal growth factor receptor (EGF-R) gene expression are inversely related in human breast cancer.
- The molecular mechanisms underlying this inverse relationship require further elucidation.
Purpose of the Study:
- To investigate the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on ER and EGF-R gene expression in MCF 7 breast cancer cells.
- To characterize the temporal dynamics of these changes.
Main Methods:
- MCF 7 cells were treated with 10 nM TPA.
- Quantitative analysis of ER and EGF-R mRNA levels over time using Northern blotting or similar techniques.
- Assessment of EGF-R protein binding.
Main Results:
- TPA treatment led to a time-dependent increase in EGF-R mRNA, observable within 3 hours and peaking between 9-24 hours.
- A concurrent decrease in ER mRNA was observed, reaching 15-20% of control levels by 12-24 hours.
- Sustained elevation of EGF-R mRNA and binding persisted up to 72 hours, accompanied by persistently reduced ER mRNA levels.
Conclusions:
- The findings support the inverse regulation of ER and EGF-R gene expression in human breast cancer.
- This study demonstrates, for the first time, that a phorbol ester can inhibit steroid hormone receptor gene expression.