Decrease in estradiol-stimulated progesterone receptor production in MCF-7 cells by epidermal growth factor and possible clinical implication for paracrine-regulated breast cancer growth

• Published in: Cancer research (Chicago, Ill.) Vol. 49; no. 3; pp. 576 - 580
• Main Authors: CORMIER, E. M, WOLF, M. F, JORDAN, V. C
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.02.1989
• Subjects: Biological and medical sciences; Breast Neoplasms - pathology; Cell Line; Epidermal Growth Factor - pharmacology; Estradiol - pharmacology; Gynecology. Andrology. Obstetrics; Humans; Kinetics; Mammary gland diseases; Medical sciences; Phenolsulfonphthalein - pharmacology; Receptors, Estrogen - metabolism; Receptors, Progesterone - biosynthesis; Tumors; Human; Hormonodependence; Estrogen; Malignant tumor; In vitro; Estradiol; Ovarian hormone; Progestagen; Mammary gland diseases; Epidermal growth factor; Tumor; Mammary gland; Progesterone; Sex steroid hormone; Tumor cell; Growth factor; Hormonal receptor
• ISSN: 0008-5472; 1538-7445

These studies have evaluated the modulation by epidermal growth factor (EGF) of estrogen receptor (ER) levels and estradiol-stimulated progesterone receptor (PgR) synthesis. Short-term culture of MCF-7 cells in an "estrogen (phenol red indicator)-free" environment caused a rise in ER concentration that is inhibited by EGF at 10(-8) M and 10(-7) M. Estradiol at 10(-10) M induced a 5-fold increase of PgR over a 5-day assay period. However, the rise in PgR was diminished or prevented by increasing concentrations of EGF (10(-9) M to 10(-7) M). Similarly, the concentration-related rise in PgR caused by estradiol (10(-13) M to 10(-9) M) was abolished after a 7-day pretreatment with EGF (10(-7) M). For both the ER and PgR receptor, EGF treatment caused a decrease in receptor number without an apparent change in receptor affinity. Thus, EGF appears to down regulate the ER by approximately 50% and to diminish the ability of estradiol to induce PgR. In addition, a survey of ER+PgR+ and ER+PgR- values of primary breast tumors from women between the ages of 55 and 70 demonstrated significantly less (50%) (85 to 39 fmol/mg of cytosol protein) ER in ER+PgR- tumors (P = 0.0005). The median PgR values for the PgR-positive tumors were 139 fmol/mg of cytosol protein. We propose that ER+ breast cancer that has changed to a paracrine growth factor-driven system (from stromal cells or ER- breast cancer cells) is less responsive to gonadal steroids. The loss of PgR in these ER+ carcinomas may be an indicator of this type of hormone independence.