Implication of PKC isoforms in reversion of mammary tumors malignancy in response to retoinc acid

MARIA I. DIAZ BESSONE; STEFANO M. CIRIGLIANO; ELISA D. BAL DE KIER JOFFE; LAURA B. TODARO; ALEJANDRO J. URTREGER

San Luis

Congreso; XLVII Reunion Anual Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular; 2011

Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular

In this work we have overeexpressed in LM3 murine mammary cells the a and d 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 PKCd overexpression induced an increase in the activity of these sites. This result correlates with previous assays showing that PKCd traslocates to the nucleus coupled to retinoid receptors. ATRA effect of was also studied in vivo and in vitro, evaluating parameters related to tumor growth and dissemination. While PKCa 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-PKCa cells also showed a higher migratory capacity, also reversed by retinoid treatment. In vivo assays showed that only PKCa 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, PKCa overexpression confers a more aggressive phenotype but make the cells sensitive to ATRA effects, while PKCd is necessary for retinoid receptors traslocation but is insufficient to alter cellular response to retinoid treatment.