Relationship between the Insulator Factors and the Methylation Status in Breast Neoplasia
Kazuhiro Nomoto, Johji Imura, Kaori Abe, Yoshiaki Uchida, Tahiko Nakajima, Shigeharu Miwa, Shinichi Hayashi, Koichi Tsuneyama. Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; Ibaraki Prefectural Central Hospital, Kasama, Ibaraki, Japan
Background: DNA methylation is related in each process of multistep carcinoma genesis and is regulated by a complex machinery that includes DNA methytransferases (DNMTs). Another regulated factor includes CCCTC-binding factor (CTCF). CTCF is a chromatin insulator with a conserved zing finger phosphoprotein that shows methylation-sensitive binding to near a promoter region. We studied the relationship between methylation status and the expression of DNMT and CTCF.
Design: Surgically resected tumors and corresponding normal tissues were collected from 91 patients diagnosed with 30 cases of invasive ductal carcinoma: Ca, 21 cases of intraductal papilloma: Pap, 31 cases of fibroadenoma: FA and 10 cases of fibrocystic disease: FD. CTCF-1, DNMT-1 and -3b were examined immunohistochemically. MSP method was used for the search of methylation status.
Results: We observed weak CTCF-1 positive reaction in FD, nuclear reaction in FA and Pap, strong cytoplasmic reaction in Ca. DNMT-1 and -3b showed a tendency to strong positive reaction in comparison with FA and Pap in Ca. The cases of Ca that CTCF-1 and DNMT-3b expressed showed the hypermethylation status.
Conclusions: The mechanism of methylation and insulator might participate mutually in the multistep carcinogenesis of the breast tissue. In this process, it is suggested that CTCF moves to cytoplasm from nucleus by methylation.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 34, Tuesday Afternoon