Walther D Zavala1, Mabel R Foscolo2, Patricia E Kunda3, Juan C Cavicchia4, Cristian G Acosta5. 1. Facultad de Odontología, Universidad Nacional de Cuyo, Mendoza, Argentina. Electronic address: wzavala@fodonto.uncu.edu.ar. 2. Instituto de Histología y Embriología de Mendoza "Dr. M. Burgos" (IHEM-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina. Electronic address: mfoscolo@fcm.uncu.edu.ar. 3. Centro Investigación Medicina Traslacional "Severo Amuchástegui" (CIMETSA), Instituto Universitario Ciencias Biomédicas Córdoba (IUCBC), Córdoba, Argentina. Electronic address: patricia.kunda@iucbc.edu.ar. 4. Instituto de Histología y Embriología de Mendoza "Dr. M. Burgos" (IHEM-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina. Electronic address: jccavic@fcm.uncu.edu.ar. 5. Instituto de Histología y Embriología de Mendoza "Dr. M. Burgos" (IHEM-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
Abstract
OBJECTIVES: Potassium channels have been proposed to promote cancer cell proliferation and metastases. Thus, we investigated the expression pattern of three 2-pore domain potassium channels (K2Ps) TASK1, TASK3 and TRESK in advanced oral squamous cell carcinoma (OSCC), the commonest oral malignancy. DESIGN: We used 4-nitroquinoline-1-oxide (4-NQO) to induce high grade OSCC in male adult rats. We then used immunohistochemistry and Western blotting to study the distribution and expression pattern of TASK1, TASK3 and TRESK in normal versus cancerous tissue. We also examined the expression of β-tubulin III (β-tub3), a marker associated with resistance to taxane-based chemotherapy and poor patient prognosis, and its correlation with the K2Ps. Finally, we studied the expression of TASK1, TASK3 and TRESK in human samples of SCC of oral origin. RESULTS: We found that TASK3 was significantly up-regulated whereas TASK1 and TRESK were both significantly down-regulated in advanced, poorly differentiated OSCC. Both, rat and human SCC showed a significant increase in the expression of β-tub3. Interestingly, the expression of the latter correlated positively and significantly with TASK3 and TRESK but not TASK1 in rat OSCC. Our initial results showed a similar pattern of up and down regulation and correlation with β-tub3 for these three K2Ps in human SCC. CONCLUSIONS: The changes in expression and the co-localization with a marker of resistance to taxanes like β-tub3 turn TASK1, TASK3 and TRESK into potentially new prognostic tools and possibly new therapeutic targets for OSCC.
OBJECTIVES: Potassium channels have been proposed to promote cancer cell proliferation and metastases. Thus, we investigated the expression pattern of three 2-pore domain potassium channels (K2Ps) TASK1, TASK3 and TRESK in advanced oral squamous cell carcinoma (OSCC), the commonest oral malignancy. DESIGN: We used 4-nitroquinoline-1-oxide (4-NQO) to induce high grade OSCC in male adult rats. We then used immunohistochemistry and Western blotting to study the distribution and expression pattern of TASK1, TASK3 and TRESK in normal versus cancerous tissue. We also examined the expression of β-tubulin III (β-tub3), a marker associated with resistance to taxane-based chemotherapy and poor patient prognosis, and its correlation with the K2Ps. Finally, we studied the expression of TASK1, TASK3 and TRESK in human samples of SCC of oral origin. RESULTS: We found that TASK3 was significantly up-regulated whereas TASK1 and TRESK were both significantly down-regulated in advanced, poorly differentiated OSCC. Both, rat and humanSCC showed a significant increase in the expression of β-tub3. Interestingly, the expression of the latter correlated positively and significantly with TASK3 and TRESK but not TASK1 in rat OSCC. Our initial results showed a similar pattern of up and down regulation and correlation with β-tub3 for these three K2Ps in humanSCC. CONCLUSIONS: The changes in expression and the co-localization with a marker of resistance to taxanes like β-tub3 turn TASK1, TASK3 and TRESK into potentially new prognostic tools and possibly new therapeutic targets for OSCC.