Catechol estrogens induce proliferation and malignant transformation in prostate epithelial cells
Mosli, Hisham A; Tolba, Mai; Al-Abd, Ahmed M; Abdel-Naim, Ashraf B;
Abstract
In the current study, the non-transformed prostatic epithelial cells (BPH-1) were exposed to the catechol estrogens (CE) 2-hydroxyestradiol (2-OHE2) or 4-hydroxyestradiol (4-OHE2), or the parent hormone 17-β-estradiol (E2) at an equimolar concentration (1μM) for a period of 6 weeks. It was found that both 2-OHE2 and 4-OHE2 have more potent proliferation-enhancing effect than E2. Exposure to 2-OHE2, 4-OHE2 or E2 resulted in a significant increase in the protein abundance of cyclin D1 and c-myc. The treated cells exhibited a shift toward the proliferative phase as indicated by FACScan. BPH-1 cells treated with 4-OHE2 showed increased abundance of estrogen receptor-α (ERα) and its downstream IGF-1R. Reduced abundance of estrogen receptor-β (ERβ) and its downstream tumor suppressor FOXO-1 were observed in cells exposed to E2, 2-OHE2 and, to a greater extent, 4-OHE2. Comet assay revealed that CE, especially 4-OHE2, elicited significant genotoxic effects as compared to E2. 4-OHE2 showed greater ability to neoplastically transform BPH-1 cells as indicated by increased colony forming capacity in soft agar and matrix invasion. In conclusion, in vitro exposure to CE could neoplastically transform human prostatic epithelial cells. Further, 4-OHE2 is more carcinogenic to prostate epithelial cells than the parent hormone E2.
Other data
Title | Catechol estrogens induce proliferation and malignant transformation in prostate epithelial cells | Authors | Mosli, Hisham A; Tolba, Mai ; Al-Abd, Ahmed M; Abdel-Naim, Ashraf B | Keywords | Carcinogenesis | Catechol estrogens | Estrogen | Prostate | Issue Date | 18-Jul-2013 | Journal | Toxicology letters | ISSN | 03784274 | DOI | 10.1016/j.toxlet.2013.05.002 | PubMed ID | 23685341 | Scopus ID | 2-s2.0-84879466593 |
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