GLUCOCORTICOID AND ESTROGEN-RECEPTORS HAVE ELEVATED ACTIVITY IN HUMANENDOMETRIAL AND OVARIAN-TUMORS AS COMPARED TO THE ADJACENT NORMAL-TISSUES AND RECOGNIZE SEQUENCE ELEMENTS OF THE H-RAS PROTOONCOGENE

We examined the level of receptor binding in H-ras elements, using nuc lear extracts derived from human endometrial and ovarian lesions and f rom adjacent normal tissue in gel retardation assays. We found increas ed binding of the glucocorticoid receptor (GR) to the H-ras GR element In more than 90% of endometrial tumors and in all ovarian tumors test ed, as compared to the corresponding adjacent normal tissue. Additiona lly, we found elevated binding of the estrogen receptor (ER) in H-ras ER element in all pairs of ovarian tumor/normal tissue tested, whereas in ER-negative control breast tumor/normal tissue pairs, no differenc es in ER DNA-binding levels were observed. These results suggest that steroid hormone receptor binding could directly activate the H-ras onc ogenic potency in human endometrial and ovarian lesions, providing add itional evidence for the role of H-ras expression in hormonally respon sive human cancers.