title: Quantitative DNA hypomethylation of ligand Jagged1 and receptor Notch1 signifies occurrence and progression of breast carcinoma.
abstract: Methylation alterations of Jagged1 and Notch1 genes have been reported in non-tumor lesions and a few cancers. However, methylation profiles of Jagged1 promoter and Notch1 exon25 in breast cancer and matched normal tissue and the association of methylation with clinicopathological characteristics still remain unclear. To explore the potential effects of aberrant DNA methylation of Jagged1 and Notch1 on occurrence and progression of breast cancer, we detected the quantitative DNA methylation of Jagged1 and Notch1 in 73 breast cancer (BC) and 20 adjacent normal breast tissues (ANBT) by using MassARRAY spectrometry. The methylation level of overall and majority individual CpG sites of the two genes were synergistically significantly lower in BC than in ANBT. The overall hypomethylation of the two genes, particularly of Jagged1 CpG_8.9.10 and Notch1 CpG_14.15.16 in primary tumors, were markedly associated with lymph node metastasis, advanced stage and high grade. The protein expressions of the both genes were examined by immunohistochemical staining in same cohorts. The expression was significantly inverse correlation with methylation. The two proteins in primary tumor were synergistically up-regulated and dramatically related to lymph node metastasis, advanced stage and high grade. Our findings suggest that the synergetic hypomethylation of Jagged1 and Notch1 genes, especially of Jagged1 CpG_8.9.10 and Notch1 CpG_14.15.16, may involve tumorigenesis and development of breast cancer. The negative relationship between methylation and expression indicates methylation role for expression regulation. The synergetic overexpression of the two proteins further indicates the effects on occurrence and progression of breast cancer.
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine Shihezi, Xinjiang, 832000, China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine Shihezi, Xinjiang, 832000, China.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine Shihezi, Xinjiang, 832000, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine Shihezi, Xinjiang, 832000, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital, Shihezi University School of Medicine Shihezi, Xinjiang, 832000, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Biochemistry and Molecular Biology, Shihezi University School of Medicine Shihezi, Xinjiang, 832000, China.
authors.forename: Zemin
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine Shihezi, Xinjiang, 832000, China.
authors.forename: Yucong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine Shihezi, Xinjiang, 832000, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine Shihezi, Xinjiang, 832000, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine Shihezi, Xinjiang, 832000, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
keywords: Jagged1; Notch1; breast cancer; expression; methylation; occurrence; progression