Int J Biol Sci 2015; 11(6):701-711. doi:10.7150/ijbs.11431 This issue
1. Department of Anatomy, Embryology Laboratory, and Brain Korea 21 plus project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea
2. Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang 410-719, Korea
3. Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Korea
4. Department of Pathology, National Health Insurance Service Ilsan Hospital, Goyang 410-719, Korea
*These authors contributed equally to this work.
HOX transcription factors play an important role in determining body patterning and cell fate during embryogenesis. Accumulating evidence has shown that these genes act as positive and/or negative modulators in many types of cancer, including breast cancer, in a tissue-specific manner. We have previously reported that HOXB5 is aberrantly overexpressed in breast cancer tissues and cell lines. Here, we investigated the biological roles and clinical relevance of HOXB5 in breast cancer. Immunohistochemical analysis of HOXB5 on tissue microarray (TMA) including 34 normal and 67 breast cancer specimens revealed that HOXB5 was highly expressed in cancer tissues, particularly from estrogen receptor (ER)-positive breast cancer patients. An online survival analysis confirmed the correlation between HOXB5 expression and poor distant metastasis-free survival in ER-positive, but not in ER-negative, breast cancer. In vitro studies indicated that HOXB5 silencing in ER-positive cells significantly decreased cell proliferation and anchorage-independent cell growth. In contrast, overexpression of HOXB5 displayed EMT characteristics with a greater invasive ability, higher cell proliferation and colony formation in soft agar. HOXB5 knockdown or overexpression led to changes in the expression levels of RET, ERBB2, and EGFR, but not of ESR1. In conclusion, we suggest that HOXB5 acts as a positive modulator most likely by promoting cell proliferative response and invasiveness in ER-positive breast cancer. These results would help predict prognosis of breast cancer and identify a new valuable therapeutic target.
Keywords: HOXB5, aberrant expression, breast cancer, ER-positive, epithelial-mesenchymal transition