Altered expression of prolactin receptor-associated signaling proteins in human breast carcinoma

Prolactin receptor signaling can modulate proliferation, survival, motility, angiogenesis, and differentiation in breast cancer. Increased serum prolactin is associated with a significantly increased risk of breast cancer in post-menopausal women. The purpose of this study was to examine the expression of prolactin receptor-associated signaling proteins in breast cancer vs benign breast tissue. Breast tissue microarrays representing 40 cases of benign and malignant pathologies were obtained from the Cooperative Human Tissue Network. Standard immunohistochemistry for prolactin and prolactin receptor-associated proteins was performed. Both positive regulators (c-Myb, Nek3, Vav2) and negative regulators (PIAS3, SIRP) of prolactin receptor signaling were examined. Virtual slides were created from the stained breast tissue microarrays. Labels were scored by region of interest and labeling indices incorporating percent target labeled and label intensity were created. Quantitative determinations of labels were made using the Clarient image system. The unpaired t-test was used to compare labels from benign and malignant tissues. Visual scoring data showed upregulation of Nek3 (P=0.000377), PIAS3 (P=0.000257), and prolactin (P=0.002576) in breast cancer vs normal/hyperplastic epithelium. c-Myb showed a trend toward upregulation, but this did not achieve statistical significance (P=0.107374). SIRP (P=0.002060) was downregulated. Vav2 showed a trend toward downregulation (P=0.107456), but this did not achieve statistical significance. Clarient analysis corroborated upregulation in cancer of Nek3 (P=0.000013), PIAS3 (P=0.000067), and prolactin (P=0.017569). In conclusion, regulators of prolactin receptor signaling show heterogeneity in their expression in benign vs malignant breast tissue. Since these species are known to regulate prolactin-mediated actions, these results suggest multiple targets for modulating prolactin receptor-mediated growth and differentiation in breast cancer.