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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
RAF Kinase Inhibitory Protein Expression and Phosphorylation Profiles in Oral Cancers
D P Hallums1, R Gomez1, A P Doyle2
1Departments of Oral and Maxillofacial Surgery, University of Texas Health Science Center at San Antonio, USA.
Abstract:
Raf Kinase Inhibitory Protein (RKIP) expression has been profiled for a number of unique tissue cancers. However, certain tissues have not been explored, and oral and oropharyngeal cancers stand out as high priority targets, given their relatively high incidence, high morbidity rate, and in many cases, preventable nature. The purpose of this study was to examine changes in RKIP expression and phosphorylation in tissues resected from oral cancer patients, and compare to results generated from immortalized cell lines raised from primary oral cancer tissues, including oral squamous cell carcinoma line 4 (SCC4) and human squamous cell carcinoma line 3 (HSC3). Out of 4 human samples collected from male and female patients across various ages with variable risk factors, we observed an across the board reduction in RKIP expression. Two human samples demonstrated a significant increase in phosphorylated RKIP when normalized to total RKIP, however all 4 were increased when normalized to total cellular protein. The immortalized oral cancer cell culture HSC3 revealed significant increases in phosphorylated RKIP with no change in total RKIP expression, while line SCC4 demonstrated an increase in both total and phosphorylated RKIP. Results presented here indicate that oral cancers behave similarly to other cancers in terms of changes in RKIP expression and phosphorylation, although immortalized cell line expression profiles significantly differ from human tissue biopsies.
Insights
Oral cancer patients show reduced Raf Kinase Inhibitory Protein (RKIP) expression. While phosphorylation patterns vary, cell lines differ significantly from patient tissues, highlighting RKIP
Area of Science:
- Oncology
- Molecular Biology
Background:
- Raf Kinase Inhibitory Protein (RKIP) is implicated in various cancers.
- Oral and oropharyngeal cancers require further investigation due to high incidence and morbidity.
Purpose of the Study:
- To analyze RKIP expression and phosphorylation in oral cancer tissues.
- To compare patient tissue findings with immortalized oral cancer cell lines (SCC4, HSC3).
Main Methods:
- Analysis of RKIP expression and phosphorylation in 4 human oral cancer tissue samples.
- Comparison with RKIP profiles in SCC4 and HSC3 cell lines.
Main Results:
- A consistent decrease in RKIP expression was observed in all human oral cancer samples.
- Increased phosphorylated RKIP was noted in human samples and HSC3 cells; SCC4 cells showed increased total and phosphorylated RKIP.
- Significant differences exist between oral cancer cell line and patient tissue RKIP profiles.
Conclusions:
- Oral cancers exhibit altered RKIP expression and phosphorylation, similar to other cancer types.
- Immortalized cell lines do not fully recapitulate RKIP changes seen in patient tissues.
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