The role of transcriptional factor Prox1 in the antiproliferative action of IFN-γ against esophageal cancer

我们先前报道了IFN-γ诱导31个食管鳞状细胞癌（ESCC）细胞系中的10个细胞凋亡。然而，IFN-γ的抗增殖作用的分子基础仍然难以捉摸。我们探讨了ESCC细胞中Prox 1和IFN-γ系统之间的联系。IFN-γ诱导ESCC细胞Prox 1表达，但在显性负性STAT 1转染的ESCC细胞中不诱导Prox 1表达。在转染Prox 1 siRNA的ESCC细胞中，IFN-γ对细胞生长的抑制作用明显受到抑制。此外，Prox 1过表达诱导ESCC细胞的抗增殖作用。我们还证明了Prox 1在原发性食管癌组织中表达（手术前接受新辅助化疗的9个样本中有5个）。这些结果表明，Prox 1可能是一个候选的目标，为新的治疗策略的食管鳞癌。

We previously reported IFN-_Y-induced apoptosis in 10 of 31 esophageal squamous cell carcinoma (ESCC) cell lines. However, the molecular basis of antiproliferative action by IFN-_Y remains elusive. We explore the link between Prox1 and the IFN-_Y system in ESCC cells. IFN-_Y induced Prox1 expression in ESCC cells but not in those transfected with dominant-negative STAT1. Cell growth inhibition by IFN-_Y was significantly suppressed in ESCC cells transfected with Prox1 siRNA. In addition, overexpression of Prox1 induced antiproliferative effect in ESCC cells. We also demonstrate that Prox1 is expressed in primary esophageal cancer tissues (five of nine samples treated with neoadjuvant chemotherapy before surgery). These results suggested that Prox1 may be a candidate target for novel therapeutic strategies of ESCCs.