Homeodomain-containing protein HOXB9 regulates expression of growth and angiogenic factors, facilitates tumor growth in vitro and is overexpressed in breast cancer tissue

FEBS J. 2012 Oct;279(19):3715-3726. doi: 10.1111/j.1742-4658.2012.08733.x. Epub 2012 Aug 31.

Abstract

HOXB9 is a homeobox-containing gene and is critical for the development of mammary gland and sternum. HOXB9 is also regulated by estrogen and is critical for angiogenesis. We investigated the biochemical roles of HOXB9 and its homeodomain in cell-cycle progression and tumorigenesis. Our studies demonstrated that HOXB9 is overexpressed in breast cancer tissue. HOXB9 overexpression stimulated 3D formation in soft agar assay. HOXB9 binds to the promoters of various tumor growth and angiogenic factors and regulates their expression. The homeodomain of HOXB9 plays crucial roles in transcriptional regulation of tumor growth factors and also in 3D colony formation, indicating crucial roles of the HOXB9 homeodomain in tumorigenesis. Overall, we demonstrated that HOXB9 is a critical regulator of tumor growth factors and is associated with tumorigenesis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiogenesis Inducing Agents / metabolism*
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Colony-Forming Units Assay
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic*
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • In Vitro Techniques
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Oligonucleotides, Antisense / pharmacology
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Array Analysis

Substances

  • Angiogenesis Inducing Agents
  • HOXB9 protein, human
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • Oligonucleotides, Antisense
  • RNA, Messenger