乳腺癌是妇女癌症死亡的首要原因。而癌症复发是乳腺癌患者死亡最常见的原因。癌症干细胞（CSC）假说的提出阐明了癌症干细胞对于乳腺癌的发展和复发至关重要。
靶向癌症干细胞与标准化疗相结合可以防止癌症复发，提高乳腺癌患者长期生存率。干细胞以非贴壁形式培养。要确定乳腺癌干细胞的分子靶点，可养人员研究了4T1小鼠乳腺癌细胞在球体形式培养或在单层细胞培养情况下干细胞相关基因的转录水平。
最明显的基因差异表达是Wnt1蛋白。功能上来说，抑制体外培养的干细胞样乳腺癌细胞株Wnt1导致包括它们球体形成能力和乙醛脱氢酶活性的降低，而增加乳腺癌细胞株Wnt1表达，干细胞样乳腺癌细胞的这些特性大大加强。
此外，在体内抑制乳腺癌细胞Wnt14T1导致干细胞样细胞形成肿瘤瘤组织能力的下降。总的来说，这些结果表明Wnt1表达可能会引起乳腺肿瘤细胞表现某些干细胞样特性。因此，针对Wnt1相关信号蛋白或许可以是一个有效的治疗晚期乳腺癌方法。（生物谷：Bioon.com）
编译自：Inhibition of Wnt1 expression reduces the enrichment of cancer stem cells in a mouse model of breast cancer
doi:10.1016/j.bbrc.2012.07.120
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PMID:
Inhibition of Wnt1 expression reduces the enrichment of cancer stem cells in a mouse model of breast cancer
A-Ram Choia,Jeong-Ran Parka,et al.
Breast cancer is the leading cause of deaths from cancer in women. Cancer recurrence is the most common cause of mortality in breast cancer patients. The cancer stem cell (CSC) hypothesis proposes that CSCs are the center of cancer development and recurrence. Targeting CSCs, in combination with standard chemotherapy, may prevent cancer recurrence and improve long-term survival. Stem cells can be enriched in non-adherent sphere cultures. To identify molecular targets in breast CSCs, we evaluated the transcription levels of stem cell-related genes in 4T1 mouse mammary cancer cells grown as spheres or in a monolayer culture. The most differentially expressed gene was found to be wingless-type MMTV integration site family member 1 (Wnt1) in the 4T1 sphere culture. Functionally, knockdown of Wnt1 in breast cancer cell lines suppressed the in vitro properties of the stem-like cells, including their sphere-forming ability and ALDH activity, whereas the addition of recombinant Wnt1 to breast cancer cell lines enhanced the in vitro properties of these stem-like cells. In addition, knockdown of Wnt1 in 4T1 cells affected the properties of the stem-like cells in vivo, including their tumorigenic potential and tumor initiation ability. Collectively, these results suggest that Wnt1 expression may give rise to the properties of CSCs in breast tumors. Therefore, targeting Wnt1-associated signaling proteins may provide an effective therapeutic approach for the treatment of advanced breast cancer. It is known that stem cells can be enriched in a non-adherent sphere culture. We compared stem cell-related genes between 4T1 cells and 4T1-derived spheres. Wnt1 was significantly up-regulated in the 4T1-derived spheres. Wnt1 regulates stem-cell like properties.
