DNA methyltransferase 1/3a overexpression in sporadic breast cancer is associated with reduced expression of estrogen receptor-alpha/breast cancer susceptibility gene 1 and poor prognosis.
DNA methyltransferases (DNMTs), including DNMT1, 3a, and 3b, play an important role in the progression of many malignant tumors. However, it remains unclear whether expression of DNMTs is associated with the development of breast cancer. This study aimed to explore the clinical significance of DNMT proteins in sporadic breast cancer. We investigated the expression of DNMT1, 3a, and 3b in 256 breast cancer and 36 breast fibroadenoma, using immunohistochemistry. The expression of DNMT1 and 3a was significantly higher in breast cancer than in fibroadenoma. In breast cancer, the expression of DNMT1 was significantly correlated with lymph node metastasis (P = 0.020), and the expression of DNMT3a and 3b was significantly correlated with advanced clinical stages (P = 0.046 and 0.012, respectively). Overexpression of DNMT1/3a was correlated with promoter hypermethylation and reduced expression of ERα and BRCA1. The expression levels of DNMT1 or DNMT3a were associated with a significantly shorter DFS or OS in a subgroup of breast cancer patients (patients with the age ≤50 years old, ERα-negative status, or HER2-postive status). The expression of DNMT1 or a combined expression of DNMT1 and 3a was associated with poor prognosis in patients who received chemotherapy and endocrine therapy, but not in patients who received chemotherapy alone. These findings suggest that DNMT1 and 3a may be involved in the progression and prognosis of sporadic breast cancer.
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.
Zhaojin
Z
Yu
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.
Qinghuan
Q
Xiao
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.
Lin
L
Zhao
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.
Jie
J
Ren
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.
Xuefeng
X
Bai
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.
Mingli
M
Sun
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.
Huizhe
H
Wu
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.|Department of Pharmacology, Basic Medical College, Liaoning Medical University, Jinzhou, China.
Xiaojian
X
Liu
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.
Zhiguo
Z
Song
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.
Yuanyuan
Y
Yan
Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
Xiaoyi
X
Mi
Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
Enhua
E
Wang
Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, China.
Feng
F
Jin
Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, Shenyang, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China.
Minjie
M
Wei
D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000032:analysis* / Q000235:genetics; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D018226:Fibroadenoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016019:Survival Analysis; D015854:Up-Regulation
D019313:BRCA1 Protein; C000717967:DNMT3A protein, human; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C000619380:DNMT1 protein, human
epigenetics; immunohistochemistry; therapy