Identification of a new proliferation-associated protein NET-1/C4.8 characteristic for a subset of high-grade cervical intraepithelial neoplasia and cervical carcinomas.

A large number of genes are known to be differentially expressed at distinct steps of carcinogenesis. By using a cell culture model system for cervical cancer, we had previously identified several genes that were more strongly expressed when comparing normal cervical epithelium with cervical intraepithelial neoplasia (CIN) and cervical cancer. In our study, we show that one of these genes, C4.8, is identical to NET-1, which is a new member of the tetraspanin family of proteins. By generating a mouse polyclonal antiserum against the major extracellular domain of the protein, we could detect NET-1/C4.8 expression both after ectopic expression of the gene in cell cultures and in cryostat sections of cervical biopsies. Moreover, immunohistochemic analyses of normal cervical epithelium, metaplasia, condyloma and CIN of different severity suggest that NET-1/C4.8 expression is associated with neoplastic cell proliferation. Notably, expression of the protein throughout the entire epithelium is only evident for a subset of CIN3. The potential importance for this gene in cervical carcinogenesis is underlined by an invariably strong expression in all undifferentiated squamous cell cancers examined. This indicates that this gene may be of prognostic value.