IBMC- Institute for Molecular and Cell Biology, I3S- Institute for Innovation and Health Research, Universidade do Porto, Portugal.
IBMC- Institute for Molecular and Cell Biology, I3S- Institute for Innovation and Health Research, Universidade do Porto, Portugal.; ICBAS- Institute of Biomedical Sciences Abel Salazar, Universidade do Porto, Portugal..
Biochim Biophys Acta Rev Cancer. 2020 Apr;1873(2):188358. doi: 10.1016/j.bbcan.2020.188358. Epub 2020 Mar 5.
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.
乳腺癌在哺乳动物成年期的乳腺中发展，被认为是第二常见的人类癌种，也是女性人群中发病率和死亡率最高的癌种。与其他人体结构不同，女性乳腺在出生后继续发育，在激素和转录因子（包括 HOX 簇编码的转录因子）的调节下，在怀孕期间、哺乳期和退化期经历各种变化。有趣的是，HOX 基因失调通常与乳腺癌的发生有关。在 HOXB 簇中，10 个基因中有 8 个在乳腺癌中表达水平改变，对其侵袭性和对激素治疗的耐药性有影响，这突出了 HOXB 基因作为潜在治疗靶点的重要性，可用于克服他莫昔芬耐药性癌症治疗的局限性。在这里，我们综述了 HOX 基因在乳腺癌中的作用的最新知识，特别关注 HOXB，讨论 HOXB 基因失调的原因和后果及其作为预后因素和治疗靶点的相关性。
