The association between c-fos and c-jun expression and estrogen and progesterone receptors is lost in human endometrial cancer

In normal human endometrium, expressions of the proto-oncogenes c-fos and c -jun parallel. We have previously shown that the expression of c-jun is rel ated to proliferation and estrogen receptor (ER) status in endometrial epit helial cells. In this study, we analyzed endometrial cancer tissues for c-f os and c-jun messenger RNA (mRNA) expression by Northern blotting. Proto-on cogene expression was compared with ER and progesterone receptor (PR) statu s and with the proliferation marker Ki-67, as well as with histological gra de and the use of hormone-replacement therapy (HRT). Messenger RNA for c-fo s was detected in 35 of 37 cancer tissues and mRNA for c-jun in 37 of 40 ti ssue samples studied. No correlation was observed between the relative mRNA levels of c-fos and c-jun, suggesting distinct control mechanisms, if any, in endometrial cancer. In contrast to normal endometrium, there was no cor relation between the proto-oncogene expression and Ki-67, ER or PR immunore activity. Neither were there any correlations between c-fos or c-jun expres sion and the histological grade of the tumor or preceding HRT. Our results reveal the loss of association between proto-oncogene expression and ovaria n steroid receptors or cell proliferation in malignant endometrium. This gi ves further support to the hypothesis that alterations in estrogen and prog esterone signalling pathways are involved in the pathogenesis of endometria l cancer.