Erk1/2 activation in stromal fibroblasts from sporadic basal cell carcinomas

Abstract

BACKGROUND Constitutive activation of the Erk pathway can lead to oncogenic transformation. However, the Erk pathway is not activated in human basal cell carcinomas (BCCs); although in animal models, this seems to be important. OBJECTIVE To help understand the role of Erk activity in BCC formation. MATERIALS AND METHODS The authors assayed the specific levels of phosphorylated Erk by immunohistochemistry in BCCs and normal skin biopsies. They have also analyzed Erk activation by immunoblot in fibroblasts isolated from BCC. RESULTS By immunohistochemical analysis, the authors have observed that 10 of BCCs (56%) did not show phosphor-Erk staining in tumor masses and 7 (40%) showed a gradient staining exhibiting phospho-Erk only in the epidermal side of tumor masses. Remarkably, 15 BCC samples (83%) showed phospho-Erk accumulation in stroma. Six of the 9 independent cultures of dermal fibroblasts isolated from BCC maintained Erk activation “in vitro.” CONCLUSION The authors propose that there is a specific cell-type regulation of Erk activity in BCC, and this feature may be relevant during BCC formation. Stroma region from BCCs showed Erk activation and reduced proliferation. Conversely, Erk activation is barely detectable in proliferative BCCs.

The authors thank Sònia Rius, Imma Montoliu, Olga Almacellas, Sònia Gatius, and Xavier Matias-Guiu for their technical assistance. They also thank the Rita Fernández, Josep M. Casanova, and Verònica Sanmart´ın for helpful discussions, sample processing, setting up protocols, and discussions, and the members of Department of Dermatology of the HUAV for helping them in collecting BCCs. This work was funded by the Spanish Ministry of Education and Science (BFU2010-20293/BMC), by the Catalan Government (SGR-559) and by the IRB Lleida.