COMPARATIVE-ANALYSIS OF THE SENSITIVITY OF ENDOMETRIAL CANCER-CELLS TO EPIDERMAL GROWTH-FACTOR AND STEROID-HORMONES

Background. Epidermal growth factor (EGF) and EGF-regulated processes play an important role in steroid signal transduction. Comparative ana lysis of EGF and steroid receptor expression and the sensitivity of ea rly stages of proliferation induction, such as activation of phospholi pid turnover to EGF and steroids, may provide a useful new approach to characterizing the sensitivity of endometrial cancer to hormone thera py. Methods. Progesterone (PR), estradiol (ER), and EGF receptor (EGFR ) content was measured by radioligand competitive methods in surgicall y excised tumors from 26 patients with primary endometrial cancer. In short term cell cultures isolated from 11 of these tumors, the influen ce of a 10-minute treatment with 10(-8)M EGF either alone or combined with 10(-8)M progesterone on P-32-incorporation into phospholipids was studied. Phospholipids were fractionated by thin-layer chromatography and were located by autoradiography, and quantification of the labele d compounds was made by densitometric scanning of the autoradiograms. Results. Epidermal growth factor receptor was found in 15 of 26 (58%) endometrial cancer samples. Eighty-two percent of the tumors studied c ontained PR, and 81% contained ER. No significant correlations were re vealed between EGFR and ER/PR status or concentration. Epidermal growt h factor stimulated P-32-incorporation by more than 120% of the contro l level in five of seven EGFR-positive and in one of four EGFR-negativ e endometrial cancer samples. An inverse relationship was revealed bet ween EGFR content and the percentage of EGF-induced stimulation of pho spholipid turnover in endometrial cancer cells (r = -0.6; P = 0.15) an d between EGFR content in EGFR-positive samples and the extent of prog esterone suppression of EGF-induced turnover (r = -0.77; P = 0.04). Co nclusions, Determination of EGF sensitivity on a receptor and a functi onal level may provide important additional information about the horm onal sensitivity of endometrial cancer.