TOX3 protein expression is correlated with pathological characteristics in breast cancer.

ABSTRACT

TOX3 is a newly identified gene that has been observed to correlate with breast cancer by genome-wide association studies (GWAS) in recent years. In addition, it has been noted that single-nucleotide polymorphisms (SNPs) in the TOX3 gene have a strong correlation with estrogen receptor (ER)-positive tumors. However, the role of TOX3 in breast carcinoma development is still unclear. There are limited studies on the subject of TOX3 mRNA expression in breast tumors and little information on the variation of TOX3 protein expression in relation to the clinical pathological features in breast cancer and healthy tissues. In this study, we characterize the protein expression of TOX3 in breast tumors with respect to various clinical and pathological characteristics and explore the correlation between TOX3 protein expression and ER-positive tumors. A breast cancer tissue microarray containing 267 human breast tumors and 25 healthy controls, breast cancer cell lines (ZR-75-1, MDA-MB-231, MCF-7 and Bcap-37) with positive or negative ER expression, tumor tissues and matched controls were used to analyze the protein expression levels of TOX3 by immunohistochemistry, western blot analysis and quantitative polymerase chain reaction. Among the 267 breast tumor specimens, ER expression was detected in 66 tumor tissues. The expression levels of TOX3 increased in breast carcinoma tissue compared with controls, and were higher in advanced carcinoma (T3 and T4), lymph node metastases tissues (N2) and stage III tissues. Furthermore, TOX3 protein expression was more intense in ER-positive tumors, but did not demonstrate a statistical significance. However, it was significantly increased in ER-positive breast cancer cell lines (ZR-75-1, MCF-7 and Bcap-37) compared with the MDA-MB-231 cell line, which had ER-negative expression. Our findings provide support to the hypothesis that TOX3 has a strong correlation with the development of breast cancer. The current study is likely to assist in investigating the mechanisms involved in breast cancer development.