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

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.