Comparative analysis of the sensitivity of endometrial cancer cells to epidermal growth factor and steroid hormones.

Abstract:

BACKGROUND:Epidermal growth factor (EGF) and EGF-regulated processes play an important role in steroid signal transduction. Comparative analysis of EGF and steroid receptor expression and the sensitivity of early stages of proliferation induction, such as activation of phospholipid turnover to EGF and steroids, may provide a useful new approach to characterizing the sensitivity of endometrial cancer to hormone therapy. METHODS:Progesterone (PR), estradiol (ER), and EGF receptor (EGFR) content was measured by radioligand competitive methods in surgically excised tumors from 26 patients with primary endometrial cancer. In short term cell cultures isolated from 11 of these tumors, the influence of a 10-minute treatment with 10(-8)M EGF either alone or combined with 10(-8)M progesterone on 32P-incorporation into phospholipids was studied. Phospholipids were fractionated by thin-layer chromatography and were located by autoradiography, and quantification of the labeled 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 contained PR, and 81% contained ER. No significant correlations were revealed between EGFR and ER/PR status or concentration. Epidermal growth factor stimulated 32P-incorporation by more than 120% of the control level in five of seven EGFR-positive and in one of four EGFR-negative endometrial cancer samples. An inverse relationship was revealed between EGFR content and the percentage of EGF-induced stimulation of phospholipid turnover in endometrial cancer cells (r = -0.6; P = 0.15) and between EGFR content in EGFR-positive samples and the extent of progesterone suppression of EGF-induced turnover (r = -0.77; P = 0.04). CONCLUSIONS:Determination of EGF sensitivity on a receptor and a functional level may provide important additional information about the hormonal sensitivity of endometrial cancer.

journal_name

Cancer

journal_title

Cancer

authors

Gershtein ES,Shatskaya VA,Kostyleva OI,Ermilova VD,Kushlinsky NE,Krasil'nikov MA

doi

10.1002/1097-0142(19951215)76:12<2524::aid-cncr282

subject

Has Abstract

pub_date

1995-12-15 00:00:00

pages

2524-9

issue

12

eissn

0008-543X

issn

1097-0142

journal_volume

76

pub_type

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