Aberrant DNA methylation of integrin α4 in human breast cancer
Autor: | Jeong Eon Lee, Eun Yoon Cho, Seok Jin Nam, Eunkyung Ko, Sung-Im Do, Duk-Hwan Kim, So Young Kang |
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Rok vydání: | 2014 |
Předmět: |
Adult
Receptor ErbB-2 Integrin alpha4 Estrogen receptor Breast Neoplasms Biology Metastasis Breast cancer Biomarkers Tumor Carcinoma medicine Humans Promoter Regions Genetic skin and connective tissue diseases Aged Neoplasm Staging Aged 80 and over Cancer General Medicine Methylation DNA Methylation Middle Aged Ductal carcinoma Prognosis medicine.disease Lymphatic Metastasis DNA methylation MCF-7 Cells Cancer research CpG Islands Female Signal Transduction |
Zdroj: | Tumor Biology. 35:7079-7084 |
ISSN: | 1423-0380 1010-4283 |
Popis: | Integrins are cell surface receptors that mediate cell-cell/extracellular interactions and have shown an association with metastasis or transformation in several cancers. However, the correlation between the clinicopathological status of breast cancer and the altered integrin α4 status is not clear. In this study, we investigated DNA methylation of integrin α4 in breast cancer. We retrieved 351 cases of surgically resected breast cancer (290 invasive carcinoma and 61 intraductal carcinoma). Methylation-specific polymerase chain reaction was performed to determine integrin α4 methylation status. Integrin α4 methylation was frequently observed in breast cancer specimens (145/351 cases, 41.3 %). In addition, DNA methylation of integrin α4 showed statistical correlation with HER2 positivity and higher histologic grade (p = 0.001, 0.008 in ductal carcinoma in situ and 0.003 in invasive ductal carcinoma). However, other clinicopathological data such as estrogen receptor, progesterone receptor, metastasis, and TNM status showed no statistical correlation. Moreover, we found that the downregulated expression of integrin α4 in a heavily methylated breast cancer cell line (ZR-75) was restored by treatment with 5-aza-2'deoxycytidine, a DNA methyltransferase inhibitor, implying transcriptional silencing by DNA methylation. We observed that integrin α4 methylation is associated with the histologic grade of tumors and lymph node metastasis. Also, this data supports a previous study that suggested integrin α4 and HER2 are involved in the same signaling pathway. DNA methylation of integrin α4 may be a poor prognostic factor which affects undifferentiated histologic change of breast cancer. |
Databáze: | OpenAIRE |
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