X-linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling

Hiroya Takeuchi, Joseph Kim, Akihide Fujimoto, Naoyuki Umetani, Takuji Mori, Anton Bilchik, Rod Turner, Andy Tran, Christine Kuo, Dave S B Hoon

研究成果: Article

47 引用 (Scopus)

抄録

Purpose: The inhibitor of the apoptosis protein (IAP) family members, such as the X-linked IAP (XIAP), survivin, and livin, are essential for cell survival and antiapoptosis in colorectal cancer cells. We hypothesized that the hepatocyte growth factor (HGF) activation in colorectal cancer via c-Met receptor regulates IAP proteins through Akt signaling. Experimental Design: The level of IAPs and C-Met mRNA expression was assessed using a quantitative real-time reverse transcriptase-PCR (RT-PCR) assay on colorectal normal mucosa (n = 13), adenomas (n = 6), and colorectal cancer tumors (n = 50). The role of HGF/C-Met pathway through Akt and XIAP was investigated by small interfering RNA (siRNA) and quantitative RT-PCR analysis of colorectal cancer lines. Results: Of the IAPs, only XIAP showed significant correlation to tumor development and progression. XIAP mRNA level in primary colorectal cancer was significantly higher than that in colorectal normal mucosa (P = 0.01); liver metastases was significantly higher than primary colorectal cancer tumors (P = 0.04); and primary colorectal cancer N1/N2 cases were significantly higher than NO cases (P = 0.008). HGF stimulation of colorectal cancer lines enhanced XIAP mRNA expression but not other IAPs. Activation of XIAP expression by HGF was inhibited by si RNA targeting Akt1 and Akt2. Conclusions: Activation of C-MET enhances XIAP through the Akt pathway. XIAP up-regulation was shown to be correlated to colorectal cancer tumor progression. The Akt-XIAP pathway may be a potential molecular target for regulating colorectal cancer progression.

元の言語English
ページ(範囲)7621-7628
ページ数8
ジャーナルClinical Cancer Research
11
発行部数21
DOI
出版物ステータスPublished - 2005 11 1
外部発表Yes

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X-Linked Inhibitor of Apoptosis Protein
Hepatocyte Growth Factor
Colorectal Neoplasms
Inhibitor of Apoptosis Proteins
Reverse Transcriptase Polymerase Chain Reaction
Messenger RNA
Mucous Membrane

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

これを引用

X-linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling. / Takeuchi, Hiroya; Kim, Joseph; Fujimoto, Akihide; Umetani, Naoyuki; Mori, Takuji; Bilchik, Anton; Turner, Rod; Tran, Andy; Kuo, Christine; Hoon, Dave S B.

:: Clinical Cancer Research, 巻 11, 番号 21, 01.11.2005, p. 7621-7628.

研究成果: Article

Takeuchi, H, Kim, J, Fujimoto, A, Umetani, N, Mori, T, Bilchik, A, Turner, R, Tran, A, Kuo, C & Hoon, DSB 2005, 'X-linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling', Clinical Cancer Research, 巻. 11, 番号 21, pp. 7621-7628. https://doi.org/10.1158/1078-0432.CCR-05-0479
Takeuchi, Hiroya ; Kim, Joseph ; Fujimoto, Akihide ; Umetani, Naoyuki ; Mori, Takuji ; Bilchik, Anton ; Turner, Rod ; Tran, Andy ; Kuo, Christine ; Hoon, Dave S B. / X-linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling. :: Clinical Cancer Research. 2005 ; 巻 11, 番号 21. pp. 7621-7628.
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abstract = "Purpose: The inhibitor of the apoptosis protein (IAP) family members, such as the X-linked IAP (XIAP), survivin, and livin, are essential for cell survival and antiapoptosis in colorectal cancer cells. We hypothesized that the hepatocyte growth factor (HGF) activation in colorectal cancer via c-Met receptor regulates IAP proteins through Akt signaling. Experimental Design: The level of IAPs and C-Met mRNA expression was assessed using a quantitative real-time reverse transcriptase-PCR (RT-PCR) assay on colorectal normal mucosa (n = 13), adenomas (n = 6), and colorectal cancer tumors (n = 50). The role of HGF/C-Met pathway through Akt and XIAP was investigated by small interfering RNA (siRNA) and quantitative RT-PCR analysis of colorectal cancer lines. Results: Of the IAPs, only XIAP showed significant correlation to tumor development and progression. XIAP mRNA level in primary colorectal cancer was significantly higher than that in colorectal normal mucosa (P = 0.01); liver metastases was significantly higher than primary colorectal cancer tumors (P = 0.04); and primary colorectal cancer N1/N2 cases were significantly higher than NO cases (P = 0.008). HGF stimulation of colorectal cancer lines enhanced XIAP mRNA expression but not other IAPs. Activation of XIAP expression by HGF was inhibited by si RNA targeting Akt1 and Akt2. Conclusions: Activation of C-MET enhances XIAP through the Akt pathway. XIAP up-regulation was shown to be correlated to colorectal cancer tumor progression. The Akt-XIAP pathway may be a potential molecular target for regulating colorectal cancer progression.",
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T1 - X-linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling

AU - Takeuchi, Hiroya

AU - Kim, Joseph

AU - Fujimoto, Akihide

AU - Umetani, Naoyuki

AU - Mori, Takuji

AU - Bilchik, Anton

AU - Turner, Rod

AU - Tran, Andy

AU - Kuo, Christine

AU - Hoon, Dave S B

PY - 2005/11/1

Y1 - 2005/11/1

N2 - Purpose: The inhibitor of the apoptosis protein (IAP) family members, such as the X-linked IAP (XIAP), survivin, and livin, are essential for cell survival and antiapoptosis in colorectal cancer cells. We hypothesized that the hepatocyte growth factor (HGF) activation in colorectal cancer via c-Met receptor regulates IAP proteins through Akt signaling. Experimental Design: The level of IAPs and C-Met mRNA expression was assessed using a quantitative real-time reverse transcriptase-PCR (RT-PCR) assay on colorectal normal mucosa (n = 13), adenomas (n = 6), and colorectal cancer tumors (n = 50). The role of HGF/C-Met pathway through Akt and XIAP was investigated by small interfering RNA (siRNA) and quantitative RT-PCR analysis of colorectal cancer lines. Results: Of the IAPs, only XIAP showed significant correlation to tumor development and progression. XIAP mRNA level in primary colorectal cancer was significantly higher than that in colorectal normal mucosa (P = 0.01); liver metastases was significantly higher than primary colorectal cancer tumors (P = 0.04); and primary colorectal cancer N1/N2 cases were significantly higher than NO cases (P = 0.008). HGF stimulation of colorectal cancer lines enhanced XIAP mRNA expression but not other IAPs. Activation of XIAP expression by HGF was inhibited by si RNA targeting Akt1 and Akt2. Conclusions: Activation of C-MET enhances XIAP through the Akt pathway. XIAP up-regulation was shown to be correlated to colorectal cancer tumor progression. The Akt-XIAP pathway may be a potential molecular target for regulating colorectal cancer progression.

AB - Purpose: The inhibitor of the apoptosis protein (IAP) family members, such as the X-linked IAP (XIAP), survivin, and livin, are essential for cell survival and antiapoptosis in colorectal cancer cells. We hypothesized that the hepatocyte growth factor (HGF) activation in colorectal cancer via c-Met receptor regulates IAP proteins through Akt signaling. Experimental Design: The level of IAPs and C-Met mRNA expression was assessed using a quantitative real-time reverse transcriptase-PCR (RT-PCR) assay on colorectal normal mucosa (n = 13), adenomas (n = 6), and colorectal cancer tumors (n = 50). The role of HGF/C-Met pathway through Akt and XIAP was investigated by small interfering RNA (siRNA) and quantitative RT-PCR analysis of colorectal cancer lines. Results: Of the IAPs, only XIAP showed significant correlation to tumor development and progression. XIAP mRNA level in primary colorectal cancer was significantly higher than that in colorectal normal mucosa (P = 0.01); liver metastases was significantly higher than primary colorectal cancer tumors (P = 0.04); and primary colorectal cancer N1/N2 cases were significantly higher than NO cases (P = 0.008). HGF stimulation of colorectal cancer lines enhanced XIAP mRNA expression but not other IAPs. Activation of XIAP expression by HGF was inhibited by si RNA targeting Akt1 and Akt2. Conclusions: Activation of C-MET enhances XIAP through the Akt pathway. XIAP up-regulation was shown to be correlated to colorectal cancer tumor progression. The Akt-XIAP pathway may be a potential molecular target for regulating colorectal cancer progression.

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