pp60c-src activation in human colon carcinoma.
Open accessAbstract
We measured the in vitro protein-tyrosine kinase activity of pp60c-src from human colon carcinoma cell lines and tumors. The activity of pp60c-src from six of nine carcinoma cell lines was higher (on average, fivefold as measured by enolase phosphorylation, or eightfold as measured by autophosphorylation) than that of pp60c-src from normal colonic mucosal cells, or human or rodent fibroblasts. Similarly, the activity of pp60c-src from 13 of 21 primary colon carcinomas was five- or sevenfold higher than that of pp60c-src from normal colonic mucosa adjacent to the tumor. The increased pp60c-src activity did not result solely from an increase in the level of pp60c-src protein, suggesting the specific activity of the pp60c-src kinase is elevated in the tumor cells. pp60c-src from colon carcinoma cells and normal colonic mucosal cells was phosphorylated at similar sites. We used immunoblotting with antibodies to phosphotyrosine to identify substrates of protein-tyrosine kinases in colonic cells. Three phosphotyrosine-containing proteins were detected at significantly higher levels in most colon carcinoma cell lines than in normal colonic mucosal cells or human or rat fibroblasts. All colon carcinoma cell lines with elevated pp60c-src in vitro kinase activity, showed increased phosphorylation of proteins on tyrosine in vivo, suggesting the presence of an activated protein-tyrosine kinase(s).
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Activation of Src family kinases occurs with high frequency during the development of colorectal cancer.
“Activation of SFKs occurs with high frequency during the development of CRC.”
From Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab (2011) · cites this paper as Cartwright et al., 1989
The Discussion reports elevated c-Src kinase activity in two-thirds of the human colon carcinoma cell lines or tumors studied, supporting the claim that activation is frequent in CRC. The paper examines c-Src specifically, not Src family kinases as a group, and does not establish when activation occurs during cancer development. The supplied copy gives no page number for the Discussion passage. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAn increase in Src family kinase activity in colorectal cancer tumors compared to normal adjacent mucosa has been reported.
“An increase in SFK activity in CRC tumors as compared to normal adjacent mucosa has been reported (Bolen et al., 1987; Cartwright et al., 1989).”
From Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab (2011) · cites this paper as Cartwright et al., 1989
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Self-citation
- Authors
- Cartwright, C. A., Kamps, M. P., Meisler, A. I., Pipas, J. M., & Eckhart, W.
- Affiliations
- Salk Institute for Biological Studies (US)
- ORCID
- Pipas, J M
- Venue
- Journal of Clinical Investigation
- Published
- 1989-06-01
- Volume
- 83
- Issue
- 6
- Pages
- 2025-2033
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC303927
- OpenAlex
- W2121881330
- Cited by
- 265
- References
- 72
- Citations by year
- 2024: 2 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 2 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 8 · 2013: 5 · 2012: 8
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 14195, CA-13884, CA-01040)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- Src kinase, tyrosine kinase, colon cancer, kinase activation, autophosphorylation, colonic mucosa, cancer cell lines, oncogene expression
- MeSH terms
- Carcinoma, Cell Line, Colonic Neoplasms, Enzyme Activation, Humans, Intestinal Mucosa, Phosphoproteins, Phosphorylation, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Retroviridae Proteins, Tumor Cells, Cultured, Tyrosine, Oncogene Protein pp60(v-src)
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