Effects of trastuzumab on epidermal growth factor receptor‐dependent and ‐independent human colon cancer cells

Kuwada, Scott K.; Scaife, Courtney L.; Kuang, Jinqiu; Li, Xiufen; Wong, Robert F.; Florell, Scott R.; Coffey, Robert J.; Gray, Phillip D.

doi:10.1002/ijc.11686

Cited by 36 publications

(29 citation statements)

References 33 publications

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“…HER-2 is an important therapeutic target in breast cancers, especially in those that greatly overexpress HER-2 protein. Colon cancer cells express much less HER-2 relative to breast cancer cells, but preclinical studies suggest that HER-2 may still be a relevant therapeutic target in human colon cancers (8,9). Inhibition of HER-2 in colon cancer cells lacking detectable integrin ␣5/␤1 expression resulted in diminished cell proliferation and tumor formation in athymic mice (9).…”

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confidence: 99%

“…Colon cancer cells express much less HER-2 relative to breast cancer cells, but preclinical studies suggest that HER-2 may still be a relevant therapeutic target in human colon cancers (8,9). Inhibition of HER-2 in colon cancer cells lacking detectable integrin ␣5/␤1 expression resulted in diminished cell proliferation and tumor formation in athymic mice (9). c-erbB-2 gene duplication appears to be an uncommon cause of HER-2 protein overexpression in colorectal cancers (10), and the post-translational regulation of HER-2 in colorectal cancers is poorly understood.…”

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confidence: 99%

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Integrin α5/β1 Expression Mediates HER-2 Down-regulation in Colon Cancer Cells

Kuwada

Kuang

2005

Journal of Biological Chemistry

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confidence: 99%

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Integrin α5/β1 Expression Mediates HER-2 Down-regulation in Colon Cancer Cells

Kuwada

Kuang

2005

Journal of Biological Chemistry

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“…We showed previously that anti-HER-2 mAb treatment of Caco-2 cells increased phospho-HER-2 levels but inhibited HER-2 tyrosine kinase activity (25). Treatment of Caco-2 cells with anti-HER-2 mAb increased phospho-HER-2 levels but diminished mH2A1 protein and mRNA levels (Fig.…”

Section: Her-2 Interacts With the Atypical Histone Macrohistone 2a1-mentioning

confidence: 56%

The Atypical Histone MacroH2A1.2 Interacts with HER-2 Protein in Cancer Cells

Kuang

et al. 2012

Journal of Biological Chemistry

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Background: HER-2/c-erbB-2 is commonly overexpressed in cancers, but how its overexpression is achieved is not well understood. Results: HER-2 was found to interact with the atypical histone macroH2A1.2. Conclusion: HER-2 cooperates with macroH2A1.2 to drive HER-2 overexpression in cancer cells. Significance: The discovery of a novel interaction between mH2A1.2 and HER-2 reveals a unique mechanism by which oncogenes can broadly deregulate gene transcription in cancer cells.

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“…Therefore, HER2 has been successfully targeted in breast cancer utilizing antibodies directed against the extracellular domains but the evidence supporting a potential role for trastuzumab in colorectal carcinoma has not been demonstrated (32). On the other hand, in experimental models, trastuzumab suppresses the growth of colon cancer cell lines with HER2 overexpression in vitro and in vivo (33).…”

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confidence: 99%

The use of protein array to identify targetable receptor tyrosine kinases for treatment of human colon cancer

Morishita

Gong²,

Nomura³

et al. 2010

Int J Oncol

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Abstract. Several studies have reported that activated receptor tyrosine kinases (RTKs) are highly expressed in colon cancer and may promote tumor growth and survival. However, there is little information available as to the function and signaling of RTKs in colon cancers. In the present study, we performed protein array technology to determine the expression status of various RTKs that are activated in colon cancer compared to normal colonic cells and tissues. Of the 42 different phospho-RTKs, 5 (ErbB2, FGFR1, FGFR2a, FGFR3 and MSPR) were activated in Caco-2, SW480, WiDr, Lovo colon cancer cell lines and cancerous tissues. In order to determine the effect of inhibition of RTKs, especially ErbB2, athymic nude mice bearing xenograft tumors were treated with the ErbB2-targeting drug trastuzumab alone, or in combination with 5-Fluorouracil (5-FU). Similar to the treatment of 5-FU alone, trastuzumab suppressed the growth of colon cancer. Combination therapy of trastuzumab and 5-FU inhibited tumor growth significantly compared to the treatment of 5-FU alone or trastuzumab alone. In addition, xenograft tumors were also analyzed by phospho-MAPK protein array. The activity of Akt3/PKBÁ was inhibited with 5-FU alone and trastuzumab, indicating that trastuzumab may inhibit colon cancer growth through ErbB2-Akt3/PKBÁ signaling. These data demonstrate that ErbB2 could be an important candidate for colon cancer therapy and the addition of trastuzumab to 5-FU therapy might augment the clinical response in colon cancer patients. Therefore, the analysis of phospho-RTK expression by protein array as a useful tool might identify novel therapies for individual patients with colon cancer.

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Effects of trastuzumab on epidermal growth factor receptor‐dependent and ‐independent human colon cancer cells

Abstract: Little information is available as to the potential role of HER-2 as a therapeutic target in colon cancers, which express much fewer HER-2 receptors than breast cancer cells.

Cited by 36 publications

References 33 publications

Integrin α5/β1 Expression Mediates HER-2 Down-regulation in Colon Cancer Cells

Integrin α5/β1 Expression Mediates HER-2 Down-regulation in Colon Cancer Cells

The Atypical Histone MacroH2A1.2 Interacts with HER-2 Protein in Cancer Cells

The use of protein array to identify targetable receptor tyrosine kinases for treatment of human colon cancer

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