Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Biol Reprod. 2013 Jul 11;89(1):10. doi: 10.1095/biolreprod.113.108001. Print 2013 Jul.
Expression of FOXC1, a forkhead box transcription factor, correlates with the human basal-like breast cancer (BLBC) subtype, and functional analyses have revealed its importance for in vitro invasiveness of BLBC cells. Women diagnosed with this breast tumor subtype have a poorer outcome because of the lack of targeted therapies; thus, continued investigation of factors driving these tumors is critical to uncover novel therapeutic targets. Several processes that dictate normal mammary morphogenesis parallel cancer progression, and enforced expression of FOXC1 can induce a progenitor state in more-differentiated mammary epithelial cells. Consequently, evaluating how FOXC1 functions in the normal gland is critical to further understand BLBC biology. Although FOXC1 is well known to control normal development of a number of tissues, its role in the mammary gland has not yet been investigated. Herein, we describe FOXC1 expression patterning in the normal breast, where it is localized to the basal/myoepithelium, suggesting that FOXC1 would be required for normal development. However, mammary glands lacking Foxc1 have no overt defect in ductal outgrowth, alveologenesis, or lineage specification. Of significant interest, we found that expression of FOXC1 is enriched in the normal luminal progenitor population, which is the postulated cell of origin of BLBC. These results indicate that FOXC1 is unnecessary for mammary morphogenesis and that its role in BLBC likely involves processes that are unrelated to cell lineage specification.
叉头框转录因子 FOXC1 的表达与人类基底样乳腺癌（BLBC）亚型相关，功能分析揭示其对 BLBC 细胞体外侵袭能力的重要性。由于缺乏靶向治疗，诊断出这种乳腺肿瘤亚型的女性预后较差；因此，继续研究驱动这些肿瘤的因素对于揭示新的治疗靶点至关重要。指导正常乳腺形态发生的几个过程与癌症进展平行，FOXC1 的强制表达可以诱导更分化的乳腺上皮细胞进入祖细胞状态。因此，评估 FOXC1 在正常腺体中的功能对于进一步了解 BLBC 生物学至关重要。尽管 FOXC1 众所周知可以控制许多组织的正常发育，但它在乳腺中的作用尚未得到研究。在此，我们描述了 FOXC1 在正常乳腺中的表达模式，其定位于基底/肌上皮，表明 FOXC1 是正常发育所必需的。然而，缺乏 Foxc1 的乳腺在导管生长、肺泡发生或谱系特化方面没有明显缺陷。值得注意的是，我们发现 FOXC1 的表达在正常腔前体细胞群中富集，这是 BLBC 的假定细胞起源。这些结果表明 FOXC1 对于乳腺形态发生不是必需的，其在 BLBC 中的作用可能涉及与细胞谱系特化无关的过程。
