Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calpactin I (annexin II) light chain gene messages were expressed in the DiFi and HT-29 human colon cancer cell lines, as well as in the diploid lung fibroblast cell line WI-38. However, expression of an approximately 1.0 kb transcript was stronger in DiFi and HT-29 cells than in WI-38 cells. The moderate to strong expression of such transcripts in DiFi and HT-29 cells indicates that the calcium binding protein, calpactin I, may be abundant in colon carcinoma cells. Calpactin I is the major substrate of pp60v-src, a tyrosine-specific protein kinase encoded by v-src, whose cellular homologue c-src also codes for a tyrosine kinase (pp60c-src), known to be activated in colon carcinomas and in cell lines derived from them (including HT-29). Abundance of calpactin I in such cells is consistent with the possibility that activation of the pp60c-src tyrosine kinase contributes to the origin of human colon cancers.
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PMID:Expression of the gene coding for the light chain of calpactin I (annexin II) in cell lines DiFi, HT-29, and WI-38. 128 33

Cell dysplasia in polyps and in ulcerative colitis are thought to be the pre-cancerous lesion leading to invasive colon cancer. Many polyps and dysplastic lesions in ulcerative colitis have phenotypic changes (blood group antigen, cytokeratins, CEA, TAG-72.3 antigen expression) and genetic changes (c-K-ras mutation, enhanced c-myc expression and pp60c-src activity) which are characteristic of invasive cancers. Thus, these early pre-cancerous lesions may be a late stage in the genetic evolution of colon cancer.
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PMID:Phenotypic and genetic alterations in pre-cancerous cells in the colon. 305 55

The activity of the protein tyrosine kinase pp60c-src was determined for each of the 60 human cell lines in the panel used by the National Cancer Institute for the random screening of potential anticancer drugs. The leukemia, lymphoma, melanoma, and small-cell lung cancer derived cell lines had low pp60c-src activity. Surprisingly, non-small-cell lung and ovarian cell lines had a median pp60c-src activity which was greater than that of the panel of cells representing colon cancer, which is most often associated with elevated pp60c-src activity. This data defines homologous cell lines which contain low and high pp60c-src activity which will aid attempts to understand the role of this enzyme in human cancer.
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PMID:Activity of pp60c-src in 60 different cell lines derived from human tumors. 753 73

The c-src proto-oncogene has been implicated in the progression of primary human colorectal carcinoma to hepatic metastasis. To determine if increased pp60c-src tyrosine kinase activity is a colon-specific phenomenon present in colorectal metastases to all sites, the pp60c-src-specific kinase activity of noncolon tumor metastases to the liver was compared to that of colorectal liver metastases. Activity of extrahepatic colon carcinoma metastases was compared to that of colorectal liver metastases as well as that of normal colonic mucosa. The specific activity of pp60c-src in multiple synchronous metastases from colon carcinoma was also examined. Tyrosine kinase activity was determined by immune complex kinase assay; protein levels were determined by immunoblotting. Specific activity was calculated for each group by dividing the total activity by protein level. Colon carcinoma metastases to the liver had significantly (P < 0.04) increased pp60c-src activity with an average 2.2-fold increase over normal mucosa. In contrast, noncolon tumor metastases to the liver showed minimal pp60c-src kinase activity. Extrahepatic colorectal metastases demonstrated significantly increased (P < 0.005) pp60c-src activity with an average 12.7-fold increase over normal mucosa. When compared to colon liver metastases, extrahepatic colorectal tumor metastases show a significant difference in activity (P < 0.05) with an average 5.7-fold increase. Examination of multiple synchronous colon carcinoma metastases confirmed these results. In summary, we conclude that (1) the activation of pp60c-src between primary tumors and metastases is specific to colon metastases, and (2) although pp60c-src activity is significantly increased in colorectal metastases, site-specific differences in the magnitude of activity are evident.
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PMID:Site-specific differences in pp60c-src activity in human colorectal metastases. 768 14

We have examined the function of the epidermal growth factor (EGF) receptor, c-Src and focal adhesion kinase (FAK) in the progression of colon cancer using an in vitro progression model. A non-tumorigenic cell line was derived from a premalignant colonic adenoma (PC/AA) from which a clonogenic variant was established (AA/C1). Following sequential treatment with sodium butyrate and the carcinogen N-methyl-N'-nitro-N-nitro-soguanidine an anchorage-independent line was isolated which, with time in culture, became tumorigenic when injected into athymic nude mice (AA/C1/SB10). We have shown that both EGF receptor and FAK protein levels were elevated in the carcinoma cells as compared to the adenoma cells, while the expression and activity of c-Src were unaltered during the adenoma to carcinoma transition. EGF induced the movement of the carcinoma cells into a reconstituted basement membrane which was not seen with the premalignant adenoma cells. This increased motility was accompanied by an EGF-induced increase in c-Src kinase activity, relocalisation of c-Src to the cell periphery and phosphorylation of FAK in the carcinoma cells but not in the adenoma cells. This suggests that c-Src plays a role in the biological behaviour of colonic carcinoma cells induced by migratory factors such as EGF, perhaps acting in conjunction with FAK to regulate focal adhesion turnover and tumour cell motility. Furthermore, although c-Src has been implicated in colonic tumour progression, we demonstrate here that in the adenoma to carcinoma in vitro model c-Src is not the driving force for this progression but co-operates with other molecules in carcinoma development.
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PMID:A role for epidermal growth factor receptor, c-Src and focal adhesion kinase in an in vitro model for the progression of colon cancer. 901 14

Whereas genetic paradigms are now defined for the development of human colon cancer, little is known regarding the mechanisms that regulate development of the metastatic phenotype. Recent reports have indirectly linked the expression and activation of c-Src to the process of human colon cancer metastasis. Whereas v-Src, a highly activated mutational derivative of c-Src, has been shown to induce metastasis, normal c-Src has not been tested for this property. We hypothesized that c-Src overexpression in the milieu of a poorly metastatic cancer cell might permit the development of a highly metastatic cell. Two poorly metastatic human colon cancer cell lines were stably transfected with expression vectors encoding normal human c-Src. Clones producing 4-10-fold more c-Src than controls were injected s.c. and intrasplenically into the nude mouse to assess primary tumor growth and liver metastatic potential. Whereas metastatic potential was unaffected, primary tumor growth in vivo was significantly enhanced by c-Src overexpression. No effects on rates of tumor cell proliferation were seen in vitro. Our findings suggest that normal c-Src may be necessary but is insufficient for the induction of the metastatic phenotype.
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PMID:Overexpression of normal c-Src in poorly metastatic human colon cancer cells enhances primary tumor growth but not metastatic potential. 941 17

Recent data suggest that signal transduction may have a critical role in the development and regulation of the metastatic phenotype. Here, we investigated the role of c-Src activation in the process of human colon cancer metastasis to the liver. Our data, derived from two different sets of human colon cancer cell line metastatic variants, suggest that not only do highly-metastatic cells display constitutively elevated c-Src protein kinase activity when compared to poorly metastatic cells, but also that receptor tyrosine kinases participate in the ligand-activation of c-Src above basal levels. Specifically, the epidermal growth factor receptor (EGFR), p185HER2/Neu and the hepatocyte growth factor receptor (c-Met) appear to be linked to the process because they preferentially activate c-Src in highly-metastatic cells. EGFR was found to associate with c-Src in colon cancer cells and specific inhibitors of the EGFR resulted in a reduction of c-Src activity to basal levels. In addition, c-Src transfectants displayed partially-activated EGFRs, suggesting a feedback role for c-Src in the regulation of the EGFR. p185HER2/Neu was also identified in immunocomplexes of c-Src following ligand activation of the EGFR, but only in highly-metastatic cells. Collectively, these observations suggest a paradigm whereby c-Src interacts with multiple cell-surface growth factors in a catalytic fashion for the development of tumor cells with metastatic potential.
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PMID:Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential. 944 56

Earlier, we have reported that N-myristoyltransferase (NMT) activity is higher in colonic epithelial neoplasms than in normal appearing colonic tissue and that increase in NMT activity appears at an early stage in colonic carcinogenesis [Magnuson, B., Raju, R. V. S., Moyana, T. N., and Sharma, R. K. (1995) J. Natl. Cancer Inst. 87, 1630-1635]. In this study, we demonstrate increased NMT mRNA in well-differentiated adenocarcinomas. NMT and c-Src mRNA levels were generally elevated in a subset of human colon cancer cell lines. Western blotting analysis employing N-myristoyltransferase inhibitory protein (NIP(71)) antibody demonstrated low levels of NIP(71) in high-expressing c-Src cell lines and high levels of NIP(71) in low-expressing c-Src cell lines. Interestingly, down regulation of c-Src by antisense expression in the HT-29 cell line resulted in increased expression of NIP(71), suggesting c-Src may negatively regulate NIP(71) expression. Furthermore, this is the first study demonstrating the expression of NIP(71) in human colon cancer cell lines and a possible relationship to colon carcinogenesis.
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PMID:Expression of N-myristoyltransferase inhibitor protein and its relationship to c-Src levels in human colon cancer cell lines. 1089 81

The non-receptor tyrosine kinase c-Src has been implicated in the development of numerous human cancers. c-Src is activated in colon cancers, particularly in highly metastatic cells, and its overexpression strongly correlates with tumor progression. C-terminal Src kinase (Csk) has been demonstrated to negatively regulate Src family tyrosine kinases through tyrosine phosphorylation at the C-terminal regulatory site (Tyr-527). We report herein that down-regulation of Src kinase activity by adenovirus-mediated csk gene transfer abrogated the highly metastatic phenotype of colon cancer cells. Overexpression of Csk decreased Src tyrosine kinase activity in NL-17 cells, the highly metastatic clone of mouse colon adenocarcinoma 26. Importantly, Csk overexpression in NL-17 cells resulted in significant suppression of in vivo metastasis, without affecting its tumorgenicity. Csk overexpression decreased the invasiveness of NL-17 cells through Matrigel, in vitro reconstituted basement membrane. Gelatin zymography confirmed the decreased protein levels of MMP-2 (gelatinase A) in the supernatants of Csk-overexpressed NL- 17 cells. These results provide a therapeutic basis for interfering with metastasis of colon cancer by csk gene-mediated down-regulation of Src kinase activity.
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PMID:Overexpression of the csk gene suppresses tumor metastasis in vivo. 1105 67

Human SRC encodes the non-receptor tyrosine kinase pp60(c-Src), which is activated in many human colon cancer cell lines (HCCLs) and tumors. We found that both c-Src protein and mRNA levels were elevated in a subset of HCCLs. Increased c-Src mRNA and protein levels correlated strongly with increased c-Src kinase activity. Nuclear run-on analysis and c-Src mRNA half-life determination demonstrated increased mRNA levels were due to increased transcription of the SRC gene. We also observed decreased c-Src mRNA stability in cell lines that displayed SRC transcriptional activation. Our findings provide the first evidence that SRC transcriptional activation is an important determinant of c-Src expression and activity in HCCLs.
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PMID:SRC transcriptional activation in a subset of human colon cancer cell lines. 1116 60


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