RGD Reference Report - The use of protein array to identify targetable receptor tyrosine kinases for treatment of human colon cancer. - Rat Genome Database

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

Authors: Morishita, Asahiro  Gong, Jian  Nomura, Takako  Yoshida, Hirohito  Izuishi, Kunihiko  Suzuki, Yasuyuki  Kushida, Yoshio  Haba, Reiji  D'Armiento, Jeanine  Masaki, Tsutomu 
Citation: Morishita A, etal., Int J Oncol. 2010 Oct;37(4):829-35.
RGD ID: 13209140
Pubmed: PMID:20811704   (View Abstract at PubMed)

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/PKBgamma was inhibited with 5-FU alone and trastuzumab, indicating that trastuzumab may inhibit colon cancer growth through ErbB2-Akt3/PKBgamma 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colon cancer treatmentIDA 13209140 RGD 
colon cancer treatmentISOAKT3 (Homo sapiens)13209140; 13209140 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Akt3  (AKT serine/threonine kinase 3)

Genes (Mus musculus)
Akt3  (thymoma viral proto-oncogene 3)

Genes (Homo sapiens)
AKT3  (AKT serine/threonine kinase 3)


Additional Information