乳腺癌是婦女癌癥死亡的首要原因。而癌癥復(fù)發(fā)是乳腺癌患者死亡最常見的原因,。癌癥干細(xì)胞（CSC）假說的提出闡明了癌癥干細(xì)胞對于乳腺癌的發(fā)展和復(fù)發(fā)至關(guān)重要。
靶向癌癥干細(xì)胞與標(biāo)準(zhǔn)化療相結(jié)合可以防止癌癥復(fù)發(fā),，提高乳腺癌患者長期生存率,。干細(xì)胞以非貼壁形式培養(yǎng)。要確定乳腺癌干細(xì)胞的分子靶點,，可養(yǎng)人員研究了4T1小鼠乳腺癌細(xì)胞在球體形式培養(yǎng)或在單層細(xì)胞培養(yǎng)情況下干細(xì)胞相關(guān)基因的轉(zhuǎn)錄水平,。
最明顯的基因差異表達(dá)是Wnt1蛋白。功能上來說,，抑制體外培養(yǎng)的干細(xì)胞樣乳腺癌細(xì)胞株Wnt1導(dǎo)致包括它們球體形成能力和乙醛脫氫酶活性的降低,，而增加乳腺癌細(xì)胞株Wnt1表達(dá)，干細(xì)胞樣乳腺癌細(xì)胞的這些特性大大加強(qiáng),。
此外,，在體內(nèi)抑制乳腺癌細(xì)胞Wnt14T1導(dǎo)致干細(xì)胞樣細(xì)胞形成腫瘤瘤組織能力的下降?？偟膩碚f,，這些結(jié)果表明Wnt1表達(dá)可能會引起乳腺腫瘤細(xì)胞表現(xiàn)某些干細(xì)胞樣特性。因此,，針對Wnt1相關(guān)信號蛋白或許可以是一個有效的治療晚期乳腺癌方法,。（生物谷：Bioon.com）
編譯自：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.
