Implication of PKC isoforms in reversion of mammary tumors malignancy in response to Retoinc Acid

DíAZ BESSONE; BERARDI; CAMPODóNICO; CIRIGLIANO; BAL; TODARO ; URTREGER

Potrero de lo Funes, San Luis

Congreso; 47 Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2011

Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

In this work we have overeexpressed in LM3 murine mammary cells the á and ä isoforms of PKC in order to study whether these genetically modified sublines are more sensitive to retinoid treatment (ATRA). Through a reporter gene assay, using the retinoic acid responsive elements upstream luciferase gene (RARE-Luciferase), we could determine that only PKCä overexpression induced an increase in the activity of these sites. This result correlates with previous assays showing that PKCä traslocates to the nucleus coupled to retinoid receptors. ATRA effect was also studied in vivo and in vitro, evaluating parameters related to tumor growth and dissemination. While PKCá overexpression induced an important increase in the in vitro proliferative capacity, only these overexpressors become sensitive to ATRA treatment showing a proliferative delay. Moreover, LM3-PKCá cells also showed a higher migratory capacity, also reversed by retinoid treatment. In vivo assays showed that only PKCá overexpression induced an increase in tumor growth and metastatic potential, and ATRA treatment was able to limit the malignant progression of these tumors. Our results suggest that, PKCá overexpression confers a more aggressive phenotype but make the cells sensitive to ATRA effects, while PKCä is necessary for retinoid receptors traslocation but is insufficient to alter cellular response to retinoid treatment.