Simultaneous Estimation of Epidermal Growth Factor Receptors and Steroid Receptors in a Series of 136 Resectable Primary Breast Tumors

Abstract

Human breast cancer cell lines, as well as human breast cancer biopsies, possess specific high-affinity epidermal growth factor receptors (EGF-r). However, reports on the presence of EGF-r in human breast cancer biopsies are still controversial, especially concerning the relationship between EGF-r and other biological variables whose prognostic relevance is well known, such as the estrogen (ER) and progesterone (PgR) receptors. In the present study, the EGF-r content was estimated in a series of 136 unselected breast cancer primaries along with cytoplasmic (ERc) and nuclear (ERn) ER and cytoplasmic PgR. EGF-binding activity consisted of a single class of high-affinity binding sites (K_d = 0.55 nM) and ranged from 0 to 275 fmol/mg protein. We observed a strong inverse association between EGF-r and ERc (p < 0.001); in fact, about two thirds of the tumors were ERc-positive/EGF-r-negative or ERc-negative/EGF-r-positive. The same type of association was found between EGF-r and either ERn or PgR.Kendall’s rank correlation test confirmed that the EGF-r concentrations were correlated with the levels of ERc (τ = -0.291, p < 0.0001), ERn (τ = -0.27, p < 0.0005) and PgR (τ = -0.162, p < 0.01). The EGF-r content was significantly higher (p < 0.0001) in the ERc-negative tumors (72.6 ± 54.4 fmol/mg protein) as compared to the ERc-positive ones (33.0 ± 37.4 fmol/mg protein). Similarly, the subset of PgR-positive tumors was characterized by lower EGF-r mean concentrations when compared to PgR-negative cases (35.4 ± 54.4 vs. 63.8 ± 54.4 fmol/mg protein). These results confirm the previously described inverse relationship between EGF-r and steroid receptors. Moreover, they suggest the existence of an interaction between steroid hormones and EGF and support the need for further studies to better understand their respective roles in modulating breast cancer growth.

The Clinical Significance of Epidermal Growth Factor Receptor (EGF-R) in Human Breast Cancer: A Review on 5232 Patients*

“…In addition, Spitzer et al (56) found higher EGF-R levels in larger tumors (>4 cm). In contrast, Cappelletti et al (38) observed that tumors larger than 3 cm were mostly EGF-R-negative, while smaller tumors (<3 cm) were almost equally distributed among the EGF-R-positive and -negative subsets. Bolla et al (50) and our group (41) found a tendency to higher EGF-R levels in Tl tumors when compared to T2 and T3 tumors, respectively.…”

“…Bolla et al (50) and our group (41) found a tendency to higher EGF-R levels in Tl tumors when compared to T2 and T3 tumors, respectively. Thus only two (25, 56) of 17 study groups found a positive correlation between tumor size and EGF-R levels, while three others (38,41,50) found a trend toward a negative relationship.…”

The two phyto-oestrogens genistein and quercetin exert different effects on oestrogen receptor function

“…Cytosolic ER and progesterone receptors (PR) were simultaneously estimated by a double-labelling DCC assay as described (Ronchi et al, 1986). Nuclear pellets were salt-extracted as described (Cappelletti et al, 1988), and cytosol and nucleosol were incubated overnight with 16α-[ 125 I]-iodo-oestradiol (8150 GBq mmol -1 , 5 nM), alone or in the presence of a 200-fold molar excess of oestradiol. Incubation was stopped by treatment with a DCC pellet.…”

Modulation of Cathepsin-D and pS2 Protein Levels in Human Breast Cancer Cell Lines

“…Cells (200-300 x 106) were homogenized by me chanical disruption to prepare subcellular fractions [16]. IGF-I and EGF receptor (IGF-I-R and EGF-R, respectively) content was determined on the crude nuclear membrane fraction using a radioligand assay as previously described [17], Steroid receptor deter minations were carried out with commercially avail able immunoenzymatic kits (ER-EIA, PR-EIA.…”