Abstract
Background
The natural estrogen 17β-estradiol (E2) functions as a potent tumor promoter during tumorigenic transformation of the mammary gland. From amongst the various pathways of E2 metabolism upregulation of C16α-hydroxylation of E2 has been associated with carcinogenesis. In the present studyin vitro andin vivo experiments were performed on estrogen receptor positive human breast cancer MCF-7 cells to examine whether the natural estrogen E2 and its metabolites 16α-hydroxyestrone (16α-OHEi) and 2-hydroxyestrone (2-OHE1) function as modulators of tumor cell growth.
Methods
An anchorage-independent growth assay was used forin vitro study by counting the number of tri-dimensional colonies formed by MCF-7 cells suspended in 0.33% agar.In vivo experiments examined the effect of implanting metabolite material pellets into female nude mice.
Results
In the anchorage-independent growth assay (AIG), continuous 14-day exposure to E2 and to 16α-OHE1 at 200 ng/ml induced a 59.4% and a 105.9% increase (P=0.001) respectively in the number of colonies of MCF-7 cells. Identical treatment with 2-OHE1, however, failed to increase AIG relative to that seen in the solvent treated control cultures. In thein vivo tumorigenicity assay, treatment of nude mice with 1.5 mg E2 or 16α-OHE1 resulted in a 335.4% and a 384.1% increase (P<0.0002) in tumor growth, while identical treatment with 2-OHE1 failed to exhibit any increase relative to the control group.
Conclusions
These results suggest that the 16α- and 2-hydroxylated metabolites of E2 may directly affectin vitro growth of MCF-7 cells via an autocrine mechanism andin vivo growth via paracrine mechanisms. Thus, E2-mediated growth regulation in MCF-7 cells may in part be due to distinct effects of specific E2 metabolites on the breast cancer cells.
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Abbreviations
- AIG:
-
Anchorage-independent growth
- Ei:
-
Estrone
- E2:
-
1 7β-Estradiol
- 2-OHE1 :
-
2-Hydroxyestrone
- 16α-OHE1 :
-
16α-Hydroxyestrone
- TGF:
-
Transforming growth factor
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Suto, A., Telang, N.T., Tanino, H. et al. In vitro andin vivo modulation of growth regulation in the human breast cancer cell line MCF-7 by estradiol metabolites. Breast Cancer 6, 87–92 (1999). https://doi.org/10.1007/BF02966913
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DOI: https://doi.org/10.1007/BF02966913