caa a22 4500 445339020 CHVBK 20180317142805.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1245/s10434-011-1683-6 doi (NATIONALLICENCE)springer-10.1245/s10434-011-1683-6 Transcriptional Factor Prox1 Plays an Essential Role in the Antiproliferative Action of Interferon-γ in Esophageal Cancer Cells [Elektronische Daten] [Masatoshi Akagami, Kenji Kawada, Hajime Kubo, Mayumi Kawada, Meiko Takahashi, Junichi Kaganoi, Shigeru Kato, Atsushi Itami, Yutaka Shimada, Go Watanabe, Yoshiharu Sakai] Background: We previously reported interferon-γ (IFN-γ)-induced apoptosis in 10 (32%) of 31 esophageal squamous cell carcinoma (ESCC) cell lines. However, the molecular basis of antiproliferative action by IFN-γ remains elusive. Here we demonstrate that IFN-γ induces transcriptional factor Prox1, and we explore the link between Prox1 and the IFN-γ system in ESCC cells. Methods: By using ESCC cell lines, we investigated the relationship between p53 mutations and the responsibility to IFN-γ, and studied the role of Prox1 in the antiproliferative effect of IFN-γ by knockdown and overexpression methods. Results: p53 mutations were found in seven of nine ESCC cell lines responsible for IFN-γ. The frequency was not different from that of p53 mutations in total ESCC cell lines (21 of 28 cell lines). Treatment of ESCC cells with IFN-β but not IFN-γ resulted in increase of p53 messenger RNA (mRNA) expression, whereas IFN-γ but not IFN-β induced cell growth inhibition of ESCCs harboring p53 mutations. IFN-γ induced Prox1 expression in ESCC cells but not in those transfected with dominant-negative STAT1. Cell growth inhibition by IFN-γ was significantly suppressed in ESCC cells transfected with Prox1 short interfering RNA (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). Conclusions: Prox1 mediates the antiproliferative effect by IFN-γ in ESCC cells. Prox1 may be a candidate target for novel therapeutic strategies of ESCCs. Society of Surgical Oncology, 2011 Akagami Masatoshi Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut Kawada Kenji Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut Kubo Hajime Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut Kawada Mayumi Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut Takahashi Meiko Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan aut Kaganoi Junichi Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut Kato Shigeru Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut Itami Atsushi Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut Shimada Yutaka Department of Surgery, Toyama University, Toyama, Japan aut Watanabe Go Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut Sakai Yoshiharu Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut Annals of Surgical Oncology Springer-Verlag 18/13(2011-12-01), 3868-3877 1068-9265 18:13<3868 2011 18 10434 https://doi.org/10.1245/s10434-011-1683-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1245/s10434-011-1683-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Akagami Masatoshi Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut NATIONALLICENCE 700 1- Kawada Kenji Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut NATIONALLICENCE 700 1- Kubo Hajime Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut NATIONALLICENCE 700 1- Kawada Mayumi Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut NATIONALLICENCE 700 1- Takahashi Meiko Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan aut NATIONALLICENCE 700 1- Kaganoi Junichi Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut NATIONALLICENCE 700 1- Kato Shigeru Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut NATIONALLICENCE 700 1- Itami Atsushi Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut NATIONALLICENCE 700 1- Shimada Yutaka Department of Surgery, Toyama University, Toyama, Japan aut NATIONALLICENCE 700 1- Watanabe Go Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut NATIONALLICENCE 700 1- Sakai Yoshiharu Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan aut NATIONALLICENCE 773 0- Annals of Surgical Oncology Springer-Verlag 18/13(2011-12-01), 3868-3877 1068-9265 18:13<3868 2011 18 10434 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer