Isoform‐specific expression of 14‐3‐3 proteins in human lung cancer tissues

Abstract

14‐3‐3 Proteins play important roles in a wide range of vital regulatory processes, including signal transduction, apoptosis, cell cycle progression and DNA replication. In mammalian cells, 7 14‐3‐3 isoforms (β, γ, ϵ, η, σ, θ and ζ) have been identified and each of these seems to have distinct tissue localizations and isoform‐specific functions. Previous studies have shown that 14‐3‐3 protein levels are higher in human lung cancers as compared to normal tissues. It is unclear, however, which of the 14‐3‐3 isoform(s) are overexpressed in these cancers. In our study, the levels of all seven 14‐3‐3 isoforms were examined by RT‐PCR and Western blotting. We show that the message for only two isoforms, 14‐3‐3ϵ and ζ, could be detected in normal tissues. In lung cancer biopsies, however, four isoforms, 14‐3‐3β, γ, σ, and θ, in addition to 14‐3‐3ϵ and ζ, were present in abundance. The expression frequency of 14‐3‐3β, γ, σ and θ isoforms was 11, 10, 13 and 8 of the 14 biopsies examined, respectively. The data from immunohistochemical staining and Western blotting were consistent with the RT‐PCR results. Given the prevalence of elevated 14‐3‐3 expression in human lung cancers we propose that these proteins may be involved in lung cancer tumorigenesis and that specific 14‐3‐3 proteins may be useful as markers for lung cancer diagnosis and targets for therapy.