Active (p)CrkL is overexpressed in human malignancies: Potential role as a surrogate parameter for therapeutic tyrosine kinase inhibition

  • Authors:
    • Christian F. Singer
    • Gernot Hudelist
    • Wolfgang Lamm
    • Ruth Mueller
    • Claudia Handl
    • Ernst Kubista
    • Klaus Czerwenka
  • View Affiliations

  • Published online on: February 1, 2006     https://doi.org/10.3892/or.15.2.353
  • Pages: 353-359
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Abstract

CrkL is a nuclear adaptor and transcriptional activator in Bcr-Abl expressing cells and constitutes the major tyrosine phosphorylated protein in CML, but the expression and biological function of CrkL in other malignancies is largely unknown. Using immunohistochemistry, we have analyzed the protein expression of activated (p)CrkL in normal and malignant tissues. We then treated K562 leukemia cells with imatinib to analyze the effect of tyrosine kinase inhibition on CrkL activation. pCrkL expression was predominantly epithelial and detected in the majority of non-malignant prostate (79%), 49% of colon biopsies, 36% of skin biopsies, and 41% of samples obtained from normal brain. Protein expression was, however, considerably less frequent in normal breast (18%), lung (16%) and ovarian (12%) tissues. In contrast to their corresponding benign tissues, pCrkL expression was significantly more common in breast cancer samples (49%, p<0.0001; Fisher's exact test), lung carcinomas (55%, p=0.0002), lymphatic tissues (80% vs. 10%, p=0.012), skin cancer (67%, p=0.020), ovarian malignomas (50%, p<0.0001) and colon carcinomas (63%, p<0.03). By contrast, activated CrkL was significantly less frequent in prostate carcinoma samples when compared to corresponding non-malignant prostatic tissues (14% vs. 79%, p<0.0001). pCrkL expression was abrogated in K562 cells with the addition of the tyrosine kinase inhibitor imatinib, which indicates that phosphorylation of CrkL is mediated through targets of therapeutic TK inhibition. We hypothesize that pCrkL is selectively up-regulated in a number of malignant tumor entities and involved in malignant transformation. We further suggest that pCrkL might serve as a potential surrogate parameter for the efficacy of therapeutic TK inhibition.

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February 2006
Volume 15 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Singer CF, Hudelist G, Lamm W, Mueller R, Handl C, Kubista E and Czerwenka K: Active (p)CrkL is overexpressed in human malignancies: Potential role as a surrogate parameter for therapeutic tyrosine kinase inhibition. Oncol Rep 15: 353-359, 2006
APA
Singer, C.F., Hudelist, G., Lamm, W., Mueller, R., Handl, C., Kubista, E., & Czerwenka, K. (2006). Active (p)CrkL is overexpressed in human malignancies: Potential role as a surrogate parameter for therapeutic tyrosine kinase inhibition. Oncology Reports, 15, 353-359. https://doi.org/10.3892/or.15.2.353
MLA
Singer, C. F., Hudelist, G., Lamm, W., Mueller, R., Handl, C., Kubista, E., Czerwenka, K."Active (p)CrkL is overexpressed in human malignancies: Potential role as a surrogate parameter for therapeutic tyrosine kinase inhibition". Oncology Reports 15.2 (2006): 353-359.
Chicago
Singer, C. F., Hudelist, G., Lamm, W., Mueller, R., Handl, C., Kubista, E., Czerwenka, K."Active (p)CrkL is overexpressed in human malignancies: Potential role as a surrogate parameter for therapeutic tyrosine kinase inhibition". Oncology Reports 15, no. 2 (2006): 353-359. https://doi.org/10.3892/or.15.2.353