7月15日,，Cancer Res雜志報(bào)道一種稱為Fra-1的因子可調(diào)節(jié)乳腺癌細(xì)胞化療敏感性，或可作為判斷乳腺癌治療預(yù)后的一項(xiàng)指標(biāo),。
Fra-1是一個(gè)Fos轉(zhuǎn)錄因子家族成員,，在多種癌癥中呈中高度表達(dá)，并在轉(zhuǎn)化,，增殖和轉(zhuǎn)移中扮演重要的角色,。
本研究發(fā)現(xiàn)Fra-1在人類II級乳腺癌組織中的表達(dá)與腫瘤化療抵抗水平呈負(fù)相關(guān)。體外研究結(jié)果發(fā)現(xiàn),，在乳腺腫瘤細(xì)胞中下調(diào)Fra-1賦予足以使這些細(xì)胞抵抗阿霉素和環(huán)磷酰胺,，而增強(qiáng)Fra-1表達(dá)，可以使這些細(xì)胞對化療敏感。
腫瘤細(xì)胞側(cè)群（side population）,，是腫瘤干細(xì)胞含量豐富的一個(gè)腫瘤細(xì)胞亞群,，與化療抵抗密切相關(guān)。Fra-1下調(diào)可在腫瘤細(xì)胞系中增加腫瘤細(xì)胞側(cè)群的比例,。相反,，F(xiàn)ra-1表達(dá)的增強(qiáng)與腫瘤細(xì)胞側(cè)群的下調(diào)相關(guān)。
相對應(yīng)的,，在體內(nèi)實(shí)驗(yàn)中,，F(xiàn)ra-1的表達(dá)增強(qiáng)可抑制腫瘤的增長。 Fra-1下調(diào)的腫瘤細(xì)胞生長速度快,，體積較大,。總之,，該研究結(jié)果表明,，F(xiàn)ra-1可能是一個(gè)重要的治療乳腺癌的預(yù)后指標(biāo)。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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Fra-1 Promotes Breast Cancer Chemosensitivity by Driving Cancer Stem Cells from Dormancy
Dan Lu1,2,Si Chen1,Xiaoyue Tan1,Na Li1,Chenghu Liu1,Zongjin Li1,Ze Liu1,Dwayne G. Stupack3,Ralph A. Reisfeld2, andRong Xiang1
Fra-1 is a member of the Fos transcription factor family that is highly expressed in multiple cancers, playing important roles in transformation, proliferation, and metastasis. In this study, we observed an inverse correlation between the expression of Fra-1 in human stage II breast cancer tissues and the corresponding level of clinical chemoresistance. Extending these findings in vitro, we found that knockdown of Fra-1 in breast tumor cells was sufficient to confer resistance to doxorubicin and cyclophosphamide, whereas enhanced Fra-1 expression could render these cells chemosensitive. The tumor cell side population, which is enriched for cancer stem cells, was found to be associated with chemoresistance. Increased side population fractions were detected among tumor cell lines subjected to Fra-1 knockdown. In contrast, enhanced expression of Fra-1 was correlated with a decreased side population fraction, and significantly, this finding was recapitulated in vivo, where tumors with enhanced expression of Fra-1 were found to have blunted growth. Tumor cells subjected to Fra-1 knockdown grew faster and were larger in size. Taken together, our findings suggest that Fra-1 may be an important prognostic marker for breast cancer therapy.
