PMID- 23685341 OWN - NLM STAT- MEDLINE DCOM- 20131113 LR - 20161125 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 220 IP - 3 DP - 2013 Jul 18 TI - Catechol estrogens induce proliferation and malignant transformation in prostate epithelial cells. PG - 247-58 LID - S0378-4274(13)00202-6 [pii] LID - 10.1016/j.toxlet.2013.05.002 [doi] AB - 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-beta-estradiol (E2) at an equimolar concentration (1muM) 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-alpha (ERalpha) and its downstream IGF-1R. Reduced abundance of estrogen receptor-beta (ERbeta) 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. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Mosli, Hisham A AU - Mosli HA AD - Department of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. FAU - Tolba, Mai F AU - Tolba MF FAU - Al-Abd, Ahmed M AU - Al-Abd AM FAU - Abdel-Naim, Ashraf B AU - Abdel-Naim AB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130515 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogen Receptor beta) RN - 0 (Estrogens, Catechol) RN - 0 (FOXO1 protein, human) RN - 0 (Forkhead Box Protein O1) RN - 0 (Forkhead Transcription Factors) RN - 4TI98Z838E (Estradiol) RN - AYU2L67YUU (2-hydroxyestradiol) RN - C3ZO03450E (4-hydroxyestradiol) RN - EC 2.7.10.1 (Receptor, IGF Type 1) SB - IM MH - Cell Cycle/drug effects MH - Cell Line MH - Cell Proliferation/drug effects MH - Cell Transformation, Neoplastic/*chemically induced/metabolism/pathology MH - Comet Assay MH - DNA Damage MH - Epithelial Cells/drug effects/pathology MH - Estradiol/*analogs & derivatives/pharmacology MH - Estrogen Receptor alpha/metabolism MH - Estrogen Receptor beta/metabolism MH - Estrogens, Catechol/*pharmacology MH - Flow Cytometry MH - Forkhead Box Protein O1 MH - Forkhead Transcription Factors/metabolism MH - Humans MH - Immunohistochemistry MH - Male MH - Prostate/*drug effects/metabolism/pathology MH - Prostatic Neoplasms/*chemically induced/metabolism/pathology MH - Receptor, IGF Type 1/metabolism EDAT- 2013/05/21 06:00 MHDA- 2013/11/14 06:00 CRDT- 2013/05/21 06:00 PHST- 2013/02/01 00:00 [received] PHST- 2013/05/03 00:00 [revised] PHST- 2013/05/06 00:00 [accepted] PHST- 2013/05/21 06:00 [entrez] PHST- 2013/05/21 06:00 [pubmed] PHST- 2013/11/14 06:00 [medline] AID - S0378-4274(13)00202-6 [pii] AID - 10.1016/j.toxlet.2013.05.002 [doi] PST - ppublish SO - Toxicol Lett. 2013 Jul 18;220(3):247-58. doi: 10.1016/j.toxlet.2013.05.002. Epub 2013 May 15.