Fra-1 promotes breast cancer chemosensitivity by driving cancer stem cells from dormancy
Menée in vitro et in vivo, cette étude suggère que le niveau d'expression du facteur de transcription Fra-1 est associé à la réponse à une chimiothérapie dans le cancer du sein
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, while enhanced Fra-1 expression could render these cells chemosensitive. The tumor cell 'side population' (SP), which is enriched for cancer stem-like cells, was found to be associated with chemoresistance. Increased SP fractions were detected among tumor cell lines subjected to Fra-1 knockdown. In contrast, enhanced expression of Fra-1 was correlated with a decreased SP 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.
Cancer Research , résumé, 2012