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.
Highlights
Proliferating cell nuclear antigen expression in non-cycling cells may be induced by growth factors in vivo
While levels of proliferating cell nuclear antigen (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
Summary
In the first set of experiments, human carcinoma cell lines (LoVo and HT29) were introduced by direct inoculation [106 cells in 0.05 ml of phosphate-buffered saline (PBS)] into the liver of nude mice. One hour later the animals (n = 6) were killed and xenografts growing in the liver were removed, fixed in formalin and processed to paraffin for both immunostaining and autoradiography. In a second set of experiments, rats were given total parenteral nutrition (TPN) with or without supplements of TGF-x or EGF for 3 days, as described previously (Goodlad et al, 1987, 1992). At the end of the experiments, animals were killed and tissues (liver and pancreas) were fixed in formalin and processed to paraffin for both immunostaining and autoradiography. PCNA immunoreactivity was identified in both sets of experiments in the same way using the monoclonal antibody PC1O by immunohistochemistry as described previously (Hall et al, 1990), except that the indirect method was employed (rather than ABC) because of the presence of high levels of biotin in the liver.
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