gastrin-releasing-peptide and Fibrocystic-Breast-Disease

Although the etiology of gross cystic disease of the breast is unknown, elevated cyst concentrations of potassium (K+) (> 60 mM/L) may be related to symptoms. The purpose of this study was to clarify the mechanism(s) of K+ accumulation in breast cysts.. We assayed cyst fluids for factors known to exert effects on K+ transport, namely, endogenous digitalis-like inhibitors of Na+,K(+)-ATPase (NKA) and the neuropeptides gastrin-releasing peptide (GRP), calcitonin (CT), and calcitonin gene-related peptide (CGRP).. Cyst fluid K+ was directly correlated with cyst volume, cyst NKA inhibitory activity (in ouabain equivalents), and cyst concentrations of calcitonin, GRP, and CGRP. Cyst fluid Na+ was inversely correlated with cyst fluid K+, cyst NKA inhibitory activity, cyst volume, and cyst fluid concentrations of calcitonin, GRP, and CGRP. NKA inhibitory activity correlated directly with GRP and CGRP. Immunocytochemistry localized GRP to breast cyst lining cells and areas of ductal and lobular epithelial hyperplasia in biopsies of 15 of 15 cysts and in 5 of 5 breast carcinomas, but not in (0 of 5) normal breast biopsies. Specificity of GRP staining was demonstrated by total abolition of reactivity after adsorption with synthetic GRP, but not after adsorption with synthetic substance P, neurokinin A, or neurokinin B.. We conclude that both the concentrations of endogenous digitalis-like factors and the neuropeptides calcitonin, GRP, and CGRP in human breast cyst fluids are related to the concentrations of K+ and Na+ in breast cysts and to cyst volume.

Topics: Adult; Biological Transport, Active; Body Fluids; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fibrocystic Breast Disease; Gastrin-Releasing Peptide; Gastrointestinal Hormones; Humans; Immunohistochemistry; Middle Aged; Neuropeptides; Peptides; Potassium; Sodium; Sodium-Potassium-Exchanging ATPase

Women with palpable breast cysts which are lined with apocrine epithelium may be at higher risk of developing breast cancer than women with breast cysts which are lined with flattened epithelium, the former group being characterized by intracystic sodium to potassium ratios below 3, while the latter group has intracystic sodium to potassium ratios above 3. In this study the distribution of intracystic concentrations of the mitogenic peptides, epidermal growth factor, endothelin and gastrin-releasing peptide in the 2 groups of breast cysts were compared to see whether differences in concentrations between the 2 cyst groups might provide an explanation for the higher risk of breast cancer observed in women with "apocrine" breast cysts. The concentrations of epidermal growth factor and gastrin-releasing peptide were significantly higher in the low electrolyte ratio group (p less than 0.001). There was no difference in endothelin concentrations between the 2 groups. Negative correlations were found between epidermal growth factor concentrations and Na+/K+ and between gastrin-releasing peptide concentrations and Na+/K+ (p less than 0.001). A positive correlation was found between gastrin-releasing peptide and epidermal growth factor concentrations in breast cyst fluid (p less than 0.001). The significantly higher intracystic concentrations of both epidermal growth factor and gastrin-releasing peptide in the low-electrolyte-ratio group may provide an explanation for the higher risk of breast cancer which has been observed in women with "apocrine" breast cysts.

Topics: Endothelins; Epidermal Growth Factor; Exudates and Transudates; Female; Fibrocystic Breast Disease; Gastrin-Releasing Peptide; Growth Substances; Humans; Peptides; Potassium; Sodium

To assess the role of growth factors in proliferative disorders of the breast, we assayed breast cyst fluid from 70 patients for calcitonin-related peptides. Cyst fluids (5.4 +/- 6.6 ml) (mean +/- SD) (n = 70) contained 10,499 +/- 8272 pg/ml of gastrin-releasing peptide (GRP)-like immunoreactivity in 66 of 70 samples. Calcitonin gene-related peptide (CGRP)-like immunoreactivity was found in 64 of 64 samples tested (3842 +/- 2048 pg/ml). Calcitonin-like immunoreactivity was detected in 47 of 69 samples (185 +/- 106 pg/ml). Significant correlations were found for GRP versus volume, CGRP, and calcitonin, for calcitonin versus volume and CGRP, and for CGRP versus volume. Extracts of two human breast carcinoma cell lines (MCF-7 and BT-20) contained measurable GRP-like immunoreactivity. We conclude that GRP-, CGRP-, and calcitonin-like immunoreactivities are present in human breast cyst fluid and that GRP-like immunoreactivity is present in two established human breast carcinoma cell lines. High concentrations of GRP-like immunoreactivity in both breast cyst fluid and breast carcinoma tissue, taken together with the known mitogenic and trophic activities of this peptide, support the hypothesis that GRP may be an important factor in human breast disease.

Topics: Biomarkers; Biomarkers, Tumor; Biopsy, Needle; Breast Neoplasms; Calcitonin; Calcitonin Gene-Related Peptide; Cell Line; Exudates and Transudates; Female; Fibrocystic Breast Disease; Gastrin-Releasing Peptide; Gastrointestinal Hormones; Humans; Peptides; Radioimmunoassay