Inhibition of P38 MAP kinase promotes tumor growth in a mouse mammary carcinoma model.

CAPOBIANCO CS; GABRI MR; BRAGADO P; AGUIRRE-GHISO J; GOMEZ DE; ALONSO DF; FARINA HG

Mendoza

Congreso; Reunión Anual de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular; 2012

Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular

Metastasis is the major cause of mortality in cancer patients. Metastatic lesions originate from disseminated tumor cells, which often undergo a period of dormancy. Little is known about the mechanisms involved in the dormancy/proliferation transition. The identification of those pathways is important for the discovery of new therapeutic targets, to prevent the recurrence after free disease periods. ERK and p38 have been suggested to present a key role in dormancy regulation: a high p38/ERK ratio results in a dormant state induction. Previously, we have shown that in vivo treatment with the p38 inhibitor SB203580 induces a shortening in the latency period for the development of F3II tumors. In a surgery model, p38 inhibition showed an increase in the multiplicity of lung metastases. The aim of this work was to evaluate the importance of p38 in the in vivo behavior of F3II, as well as its role in the regulation of ERK activity. Tumor-bearing mice were subjected to partial surgical excision, leaving a residual tumor piece. Ten days post-surgery mice were treated with SB203580. This resulted in the development of larger tumor recurrences compared to the control group. We also treated F3II cells with SB203580 in vitro and this resulted in ERK activation. Taken together, these results suggest that p38 and ERK are important regulators in tumor dormancy in mammary carcinoma.