4-hydroxy estrogen induces DNA damage on codon 130/131 of PTEN in endometrial carcinoma cells. (15th January 2015)

• Record Type: Journal Article
• Authors: Ke, He; Suzuki, Akihisa; Miyamoto, Tsutomu; Kashima, Hiroyasu; Shiozawa, Tanri
• Is Part Of: Molecular and cellular endocrinology. Volume 400(2015)
• Page Start: 71
• Page End: 77
• Publication Date: 2015-01-15
• Subjects: Estrogen metabolite -- DNA damage -- PTEN -- Endometrial carcinoma -- TDPCR; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2014.10.027
• Languages: English
• ISSNs: 0303-7207

Abstract

Highlights: We improved the TDPCR method to detect DNA damage using a capillary sequencer. This method detected 4-OHE2-induced DNA damages at the specific DNA sites. Four-OHE2 induced DNA damage on codon 130/131 of PTEN in endometrial cells. Estradiol did not induce DNA damage in exon 5 of PTEN . Both estradiol and 4-OHE2 did not affect MSI status in endometrial cells. Abstract: Catechol estrogens, such as 4-hydroxyestradiol (4-OHE2), are estrogen metabolites that form DNA adducts and may induce mutations and subsequent cell transformation in mammary cells; however, little is known about their roles in endometrial carcinogenesis. Furthermore, it remains unclear whether 4-OHE2 is able to induce DNA damage on specific genes involved in carcinogenesis or a 'pro'-mutation status such as microsatellite instability (MSI). Therefore, we modified terminal transferase-dependent PCR by the application of a capillary sequencer to detect DNA damage at the single base level. Using this method, we demonstrated that 4-OHE2 directly induced DNA damage on codon 130/131 in exon 5 of PTEN, which is a mutation hot spot for PTEN in endometrial carcinoma. Whereas, both estradiol and 4-OHE2 treatment did not affect MSI status in immortalized endometrial glandular cells. 4-OHE2 might contribute to endometrial carcinogenesis by inducing PTEN mutation on codon 130/131.