title: 4-hydroxy estrogen induces DNA damage on codon 130/131 of PTEN in endometrial carcinoma 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.
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, 1 Zhongshan 2nd Road, Yuexiu, Guangzhou, Guangdong, China.
authors.forename: He
authors.initials: H
authors.lastname: Ke
authors.affiliation: Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan; Department of Obstetrics and Gynecology, Iida Municipal Hospital, 438 Yawatamachi, Iida 395-8502, Japan. Electronic address: suzuaki50@gmail.com.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kashima
authors.affiliation: Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors.forename: Tanri
authors.initials: T
authors.lastname: Shiozawa
mesh_terms: D001483:Base Sequence; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003062:Codon; D018736:DNA Adducts / Q000737:chemistry; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002393:Estrogens, Catechol / Q000737:chemistry / Q000494:pharmacology*; D005091:Exons; D005260:Female; D015870:Gene Expression; D006801:Humans; D053842:Microsatellite Instability / Q000187:drug effects; D008969:Molecular Sequence Data; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: D003062:Codon; D018736:DNA Adducts; D002393:Estrogens, Catechol; C014036:4-hydroxyestradiol; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: DNA damage; Endometrial carcinoma; Estrogen metabolite; PTEN; TDPCR