Background: 14-3-3σ is down-regulated in a large proportion of basal cell carcinomas (BCC). IkappaB kinase α (IKK-α), one of the two catalytic subunits of the IKK complex involved in NF-kappaB-activation, also functions as a modulator of epidermal development and differentiation. Down-regulation of IKK-α causes hyperplasia and promotes skin cancer. IKK-α has been found to regulate the expression of 14-3-3σ by shielding its promoter from hypermethylation and thereby preventing its silencing in mouse keratinocytes.
Objectives: To evaluate the potential role of IKK-α in the silencing of 14-3-3σ in basal cell carcinoma.
Materials and methods: Expression of 14-3-3σ and IKK-α was studied by immunohistochemistry in 33 sporadic BCCs and 26 BCCs from patients with basal cell nevus syndrome (BCNS).
Results: Marked reduction or absence of 14-3-3σ was found in 24 (92%) BCCs from BCNS patients, and in 29 (88%) sporadic BCCs. Marked reduction or absence of IKK-α was found in 22 (85%) BCCs from patients with BCNS, and in 27 (82%) sporadic BCCs. Expression levels for 14-3-3σ and IKK-α correlated positively in 92% of BCCs from BCNS patients, and in 85% of sporadic BCCs.
Conclusions: Our findings suggest that down-regulation of IKK-α is required for 14-3-3σ promoter methylation and silencing in the pathogenesis of BCC. Besides, our observation that 14-3-3σ silencing is also frequently found in BCC from patients with BCNS suggests a possible link between the sonic hedgehog/patched and 14-3-3σ/IKK-α pathways.
© 2013 European Academy of Dermatology and Venereology.