HOX genes function in Breast Cancer development

Biochim Biophys Acta Rev Cancer. 2020 Apr;1873(2):188358. doi: 10.1016/j.bbcan.2020.188358. Epub 2020 Mar 5.

Abstract

Breast cancer develops in the mammary glands during mammalian adulthood and is considered the second most common type of human carcinoma and the most incident and mortal in the female population. In contrast to other human structures, the female mammary glands continue to develop after birth, undergoing various modifications during pregnancy, lactation and involution under the regulation of hormones and transcription factors, including those encoded by the HOX clusters (A, B, C, and D). Interestingly, HOX gene deregulation is often associated to breast cancer development. Within the HOXB cluster, 8 out of the 10 genes present altered expression levels in breast cancer with an impact in its aggressiveness and resistance to hormone therapy, which highlights the importance of HOXB genes as potential therapeutic targets used to overcome the limitations of tamoxifen-resistant cancer treatments. Here, we review the current state of knowledge on the role of HOX genes in breast cancer, specially focus on HOXB, discussing the causes and consequences of HOXB gene deregulation and their relevance as prognostic factors and therapeutic targets.

Keywords: Breast Cancer; HOX clusters; HOXB genes; Mammary glands; Molecular subtypes; Therapeutic targets; Transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Disease Models, Animal
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Developmental*
  • Gene Expression Regulation, Neoplastic*
  • Genes, Homeobox
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / pathology
  • Mammary Glands, Human / growth & development
  • Mammary Glands, Human / pathology*
  • Neoplasm Staging
  • Pregnancy
  • Prognosis

Substances

  • Antineoplastic Agents, Hormonal
  • Homeodomain Proteins