p63-controlled gene expression profiles implicated in epithelial-mesenchymal transition

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590380
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KURATA Shunichi Tokyo Medical and Dental University, 難治疾患研究所, 准教授 (60140901)
• Co-Investigator(Renkei-kenkyūsha): KATOH Iyoko 山梨大学, 医学工学総合研究部, 准教授 (20333297)
• Project Period (FY): 2008 – 2010
• Keywords: 細胞 / 扁平上皮癌 / p63

Research Abstract

To understand the functions of p63 in squamous cell carcinomas (SCC) and the malignant progression, we performed gene expression profiling after p63 silencing in cell lines. Cellular signaling mechanisms that induce p63 and block the malignant conversion were also studied. p63-knockdown cells showed loss of varied gene expression for epithelial cell adhesion and keratinocyte differentiation. Increases in gene expression associated with malignant cancers were also detected, suggesting epithelial-mesenchymal transition (EMT)-like events. Furthermore, we determined that Np63 is induced by the keratinocyte-specific TGF- signaling with IKK . The mutual induction between p63 and IKK and the transcriptional control in each system may altogether block the gain of invasive phenotype in early phase SCC.

Research Products

• [Journal Article] Induction of ΔNp63 by the newly identified keratinocyte-specific transforming growth factor β Signaling Pathway with Smad2 and IκB Kinase α in squamous cell carcinoma. (2010)
  • Author(s): Fukunishi N, Katoh I, Tomimori Y, Tsukinoki K, Hata R, Nakao A, Ikawa Y, Kurata S.
  • Journal Title: Neoplasia. 12(12) Pages: 969-979
  • Peer Reviewed
• [Journal Article] Lung-lung interaction in isolated perfused unilateral hyperventilated rat lungs. (2010)
  • Author(s): Bilali A, Kurata S, Ikeda S, Georgieva GS, Zhu C, Tomita M, Katoh I, Mitaka C, Eishi Y, Imai T.
  • Journal Title: Transl Res. 155(5) Pages: 228-237
  • Peer Reviewed
• [Journal Article] Salvage of nonischemic control lung from injury by unilateral ischemic lung with apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, in isolated perfused rat lung. (2008)
  • Author(s): Zhu C, Bilali A, Georgieva GS, Kurata S, Mitaka C, Imai T.
  • Journal Title: Transl Res. 152(6) Pages: 273-282
  • Peer Reviewed
• [Journal Article] Apaf-1-deficient fog mouse cell apoptosis involves hypo-polarization of the mitochondrial inner membrane, ATP depletion and citrate accumulation. (2008)
  • Author(s): Katoh I, Sato S, Fukunishi N, Yoshida H, Imai T, Kurata S.
  • Journal Title: Cell Res. 18(12) Pages: 1210-1219
  • Peer Reviewed
• [Journal Article] p63(TP63) elicits strong trans-activation of the MFG-E8/lactadherin/BA46 gene through interactions between the TA and DeltaN isoforms. (2008)
  • Author(s): Okuyama T, Kurata S, Tomimori Y, Fukunishi N, Sato S, Osada M, Tsukinoki K, Jin HF, Yamashita A, Ito M, Kobayashi S, Hata RI, Ikawa Y, Katoh I.
  • Journal Title: Oncogene. 27(3) Pages: 308-317
  • Peer Reviewed
• [Presentation] Induction of p63 by the keratinocyte-specific TGF-beta signaling pathway in squamous cell carcinomas. (2010)
  • Author(s): 福西菜穂子, 他
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-23
• [Presentation] Induction of human endogenous retrovirus-K (HERV-K) LTR in melanomas by MITF, a melanogenesis transcription factor. (2010)
  • Author(s): Katoh, I., 他
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-22
• [Presentation] p63のΔNプロモータはケラチノサイト特異的な新規TGF-βシグナルの標的である (2009)
  • Author(s): 福西菜穂子, 他
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Presentation] (インターナショナルセッション)DeltaN-p63 is inducible by Smad2 and IKKalpha, the newly identified keratinocyte-specific TGF-beta signaling partners (2009)
  • Author(s): Katoh, I., 他
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: Pacifico Yokohama,横浜
  • Year and Date: 2009-10-01
• [Presentation] p63 promote proliferation of squamous cell carcinomas through a novel pathway of PP2A and GSK-3beta (2009)
  • Author(s): 福西菜穂子, 他
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: Pacifico Yokohama,横浜
  • Year and Date: 2009-10-01
• [Presentation] High tidal volume(TV) ventilation induced cytokine mRNA and edema in hyperventilated lung in isolated perfused unilateral hyperventilated Rat lung. (2008)
  • Author(s): Aishan B, 他
  • Organizer: 37^<th> congress of Critical Care Med.
  • Place of Presentation: (Oral)Miami
  • Year and Date: 20080400
• [Presentation] ミトコンドリアのメタボリック経路によるアポトーシス制御 (2008)
  • Author(s): 倉田俊一, 他
  • Organizer: 第81回日本生化学会(分子生物との合同会議)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] p63による扁平上皮癌細胞の増殖抑制:ERK(MAPK)の関与 (2008)
  • Author(s): 福西菜穂子, 他
  • Organizer: 第81回日本生化学会(分子生物との合同会議)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] Apaf-1-independent mitochondrial in situ caspase-9 activation. (2008)
  • Author(s): 倉田俊一, 他
  • Organizer: 第67回日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Sustained ERK-1 (MAPK) phosphorylation in carcinoma cells with p63-silencing.(Iyoko Katoh, Youji Ikawa, Ryu-ichiro Hata, Shunichi Kurata) (2008)
  • Author(s): 福西菜穂子, 他
  • Organizer: 第67 回日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Ameliorating effect of combination of NADPH oxidase inhibitor (apocynin) and TNF α converting enzyme inhibitor on ischemia/reperfusion (I/R) injury. (2008)
  • Author(s): Chenting Z., Aishan B, 他
  • Organizer: 37^<th> congress of Critical Care Med.
  • Place of Presentation: Miami
  • Year and Date: 2008-04-18
• [Remarks] ホームページ等