BRAF and RKIP are significantly decreased in cutaneous squamous cell carcinoma
Spandidos, Demetrios A.
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Background: Actinic keratosis (AK) is a well-established pre-cancerous skin lesion that has the potential to progress to squamous cell carcinoma (SCC). However, little is known about the implication of BRAF and RKIP expression, or about the incidence of BRAF mutations in the formation of these cutaneous diseases. The RAS oncogene has been proposed to significantly contribute to skin cancer development. Moreover, numerous BRAF mutations have been detected in melanoma biopsy specimens and cell lines. Objectives: This study aimed to measure the mRNA levels of the genes BRAF and RKIP in AK, as well as their possible implication in the progress of AK to SCC. All biopsy specimens were also screened for BRAF mutations within exons 11 and 15. Results: Significant downregulation was noted for both genes in SCC, compared to normal tissue (for BRAF, p = 0.002; for RKIP, p < 0.001). RKIP expression levels were significantly higher than the corresponding levels of BRAF (p < 0.001), whereas the two genes showed a negative correlation not only in AK and SCC, but in the adjacent phenotypically normal skin tissue, as well. No mutation was detected, either in AK or SCC, within exons 11 and 15 of the BRAF gene. Patients and methods: Expression levels of the genes BRAF and RKIP were examined in 16 AKs and 12 SCCs by RT-qPCR. A novel allele-specific qPCR method, in combination with direct DNA sequencing, was performed in order to inspect the frequency of the V600E mutation in exon 15, as well as to examine the mutation status of the gene within exon 11. Conclusion: Both BRAF and RKIP expression levels exhibit a decrease from normal skin tissue and AK, going to SCC. The decrease of RKIP mRNA levels in SCC, suggests one novel mechanism in the deregulation of the BRAF signaling pathway. Our results further indicate that BRAF does not appear to be frequently mutated either in pre-cancerous skin lesions (AK) or in non-melanoma skin tumors (SCC).