HOXB5 acts as a positive modulator in breast cancer biology

Abstract

HOX genes are part of group of homeobox genes and play an important role in determining body patterning and cell fate during embryogenesis. There has been accumulating evidence that these genes act as positive or negative modulators in several cancers, including breast cancer, in a tissue specific manner. Recently, it was found that HOXB5 is aberrantly overexpressed in certain breast cancer cell lines and breast cancer tissues. There had not yet been a study investigating the effect of HOXB5 on breast cancer biology. Therefore, I aimed to investigate the role of HOXB5 in breast cancer biology and to evaluate the clinical significance of this gene. To investigate the effect of HOXB5 on breast cancer biology, breast cancer cell line T47D, in which HOXB5 is highly expressed, was transfected with HOXB5 shRNA and nonspecific shRNA by using a lentiviral particle system, and stable cell lines were obtained. Then, the MTT assay to assess proliferation, the soft agar colony formation assay to assess anchorage-independent growth, and the Matrigel invasion assay to assess invasive ability were performed. For overexpression experiments, stable cell lines were generated from MCF7 cells and the MTT assay, the soft agar colony formation assay, and the Matrigel invasion assay were conducted. To evaluate the clinical significance of HOXB5, clinical information and tissues obtained from breast cancer patients as well as online tools were used. This study showed that HOXB5 was highly expressed in some breast cancer tissues, especially in estrogen receptor positive breast cancer tissues at both the mRNA and protein levels. HOXB5 knockdown inhibited the proliferation and anchorage- independent growth of T47D cells, but had no effect on their invasive ability. Ectopic HOXB5 expression promoted the proliferation, anchorage-independent growth, and invasive ability of MCF7 cells. Higher

expression of HOXB5 was associated with poor distant metastasis-free survival and a poor response to endocrine therapy in estrogen receptor positive breast cancers. In conclusion, I suggest that HOXB5 acts as a positive modulator in breast cancer biology and higher expression of HOXB5 is a poor prognostic factor for ER positive breast cancer.