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

我们先前报道了在31个食管鳞状细胞癌(ESCC)细胞系中，有10个细胞系在干扰素-γ诱导下发生了细胞凋亡。然而，干扰素-γ抗增殖作用的分子基础仍不清楚。我们探讨了Prox1与ESCC细胞中的干扰素-γ系统之间的联系。干扰素-γ可诱导ESCC细胞Prox1的表达，但对显性阴性STAT1基因转染者无明显影响。在转染Prox1 siRNA的ESCC细胞中，干扰素-Y对细胞生长的抑制作用明显增强。此外，Prox1过表达还可诱导ESCC细胞的增殖抑制作用。我们还证明Prox1在原发食道癌组织中表达(手术前接受新辅助化疗的9个样本中有5个)。这些结果提示Prox1可能是食管癌新的治疗策略的候选靶点。

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.