Cancer Res：Fra-1因子或成为治疗乳腺癌的预后指标

7月15日，Cancer Res杂志报道一种称为Fra-1的因子可调节乳腺癌细胞化疗敏感性，或可作为判断乳腺癌治疗预后的一项指标。

Fra-1是一个Fos转录因子家族成员，在多种癌症中呈中高度表达，并在转化，增殖和转移中扮演重要的角色。

本研究发现Fra-1在人类II级乳腺癌组织中的表达与肿瘤化疗抵抗水平呈负相关。体外研究结果发现，在乳腺肿瘤细胞中下调Fra-1赋予足以使这些细胞抵抗阿霉素和环磷酰胺，而增强Fra-1表达，可以使这些细胞对化疗敏感。

肿瘤细胞侧群（side population），是肿瘤干细胞含量丰富的一个肿瘤细胞亚群，与化疗抵抗密切相关。Fra-1下调可在肿瘤细胞系中增加肿瘤细胞侧群的比例。相反，Fra-1表达的增强与肿瘤细胞侧群的下调相关。

相对应的，在体内实验中，Fra-1的表达增强可抑制肿瘤的增长。 Fra-1下调的肿瘤细胞生长速度快，体积较大。总之，该研究结果表明，Fra-1可能是一个重要的治疗乳腺癌的预后指标。

doi:10.1016/j.cell.2011.10.017
PMC:
PMID:

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.