title: HOXB5 Promotes the Proliferation and Invasion of Breast Cancer Cells.
abstract: 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.
authors.affiliation: 1. Department of Anatomy, Embryology Laboratory, and Brain Korea 21 plus project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Ho
authors.initials: H
authors.lastname: Hur
authors.affiliation: 1. Department of Anatomy, Embryology Laboratory, and Brain Korea 21 plus project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Yun
authors.affiliation: 4. Department of Pathology, National Health Insurance Service Ilsan Hospital, Goyang 410-719, Korea.
authors.forename: Yeejeong
authors.initials: Y
authors.lastname: Kim
authors.affiliation: 1. Department of Anatomy, Embryology Laboratory, and Brain Korea 21 plus project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Seoyeon
authors.initials: S
authors.lastname: Yang
authors.affiliation: 3. Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Seung Il
authors.initials: SI
authors.lastname: Kim
authors.affiliation: 1. Department of Anatomy, Embryology Laboratory, and Brain Korea 21 plus project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Kim
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness / Q000235:genetics
chemical_list: C489126:HOXB5 protein, human; D018398:Homeodomain Proteins
keywords: ER-positive; HOXB5; aberrant expression; breast cancer; epithelial-mesenchymal transition