Proliferating cell nuclear antigen expression in non-cycling cells may be induced by growth factors in vivo

Abstract

The proliferating cell nuclear antigen (PCNA) is required for DNA replication and DNA nucleotide excision repair. Considerable evidence points to PCNA expression being a marker of proliferation in many situations. However, while levels of PCNA are normally very low in non-cycling tissues, high levels of the protein have been observed in the normal tissues surrounding human breast and pancreatic tumours. Using two model systems we have shown that PCNA is induced in non-cycling cells by adjacent transplanted tumour cells and that this phenomenon may be mimicked by the in vivo administration of growth factors (transforming growth factor alpha and epidermal growth factor). These data suggest that tumours may elaborate factors that induce PCNA expression in nearby normal cells. PCNA induction the normal cells surrounding tumours is a direct example of the effect of tumour cells on normal surrounding tissues. This effect may prove to be a useful parameter in the analysis of tumour-host interactions.