Transcriptional effects of Organochlorine o,p′-DDT and its Metabolite p,p′-DDE in Transfected MDA-MB 231 and MCF-7 Breast Cancer Cell Lines

• Main Authors: Ehsan zayerzadeh, Mohammad Kazem Koohi, Azadeh Fardipour
• Format: Article
• Language: English
• Published: Mazandaran University of Medical Sciences and Health Services 2015-04-01
• Series: Research in Molecular Medicine
• Subjects: Organochlorinated pesticides; o; p’-DDT; MCF-7 cell line; thymidine kinase-ERE promoter.
• Online Access: http://rmm.mazums.ac.ir/browse.php?a_code=A-10-683-4&slc_lang=en&sid=1

Background: The organochlorine DDT has estrogenic activity but the mechanism underlying the estrogenic activity of this pesticide remains unclear. In the present investigation here, we studied the transcriptional effects of a synthetic organochlorine pesticide o,p’-DDT [1.1.1.-trichloro-2-(o-chlorophenyl)-2-p-chloriphenyl ethane] and its metabolite p,p'-DDE (2-2-bis(4/chlorophenyl)-1-1-dichloroethyl) on the bovine oxytocin and the thymidine kinase-ERE promoter by estrogen receptor &alpha in MDA-MB 231 and MCF-7 breast cancer cell line. Materials and Methods: Cells were seeded for transfections into 12- well plates at a density of 100000 cells per well and were transfected with a total of 3 &mug of plasmid DNA using calcium phosphate coprecipitation. o,p’-DDT and p,p'-DDE were used for stimulation of transfected MDA-MB 231 and MCF-7 breast cancer cell lines. Results: The results showed o,p’-DDT has no agonistic activity in MDA-MB 231 cells transfected with the oxytocin promoter construct (OTwt) or the thymidine kinase-ERE promoter construct (TK ERE) and estrogen receptor &alpha. While, The results obviously show that o,p’-DDT has an agonistic effect on both the oxytocin and the thymidine kinase-ERE promoter in MCF-7 leading to a more than two-fold stimulation of transcription at 10-5 M. In addition, there is no agonistic effect with p,p'-DDE on transfected MCF-7 cells and MDA-MB 231 cell line. Conclusion: In conclusion, our results revealed that o,p’-DDT has not estrogenic activity in a classical mechanism in transfected MDA-MB 231 breast cancer cells while has estrogenic activity in a classical mechanism in transfected MCF-7 human breast cancer cell line.