Title: Novel roles of prolactin and estrogens in breast cancer: resistance to chemotherapy.
Authors: LaPensee, Elizabeth W; Ben-Jonathan, Nira
Published In Endocr Relat Cancer, (2010 Jun)
Abstract: Resistance to chemotherapy is a major complication in the treatment of advanced breast cancer. Estrogens and prolactin (PRL) are implicated in the pathogenesis of breast cancer but their roles in chemoresistance have been overlooked. A common feature to the two hormones is activation of their receptors by diverse compounds, which mimic or antagonize their actions. The PRL receptor is activated by lactogens (PRL, GH, or placental lactogen) originating from the pituitary, breast, adipose tissue, or the placenta. Estrogen receptors exist in multiple membrane-associated and cytoplasmic forms that can be activated by endogenous estrogens, man-made chemicals, and phytoestrogens. Here, we review evidence that low doses of PRL, estradiol (E(2)), and bisphenol A (BPA) antagonize multiple anticancer drugs that induce cell death by different mechanisms. Focusing on cisplatin, a DNA-damaging drug which is effective in the treatment of many cancer types but not breast cancer, we compare the abilities of PRL, E(2), and BPA to antagonize its cytotoxicity. Whereas PRL acts by activating the glutathione-S-transferase detoxification enzyme, E(2) and BPA act by inducing the antiapoptotic protein Bcl-2. The implications of these findings to patients undergoing chemotherapy are discussed.
PubMed ID: 20071456
MeSH Terms: Antineoplastic Agents/pharmacology; Antineoplastic Agents/therapeutic use; Apoptosis/drug effects; Breast Neoplasms/drug therapy*; Breast Neoplasms/metabolism; Cisplatin/pharmacology; Cisplatin/therapeutic use; Drug Resistance, Neoplasm*; Estradiol/metabolism*; Estradiol/pharmacology; Female; Genes, bcl-2/drug effects; Glutathione Transferase/metabolism; Glutathione Transferase/pharmacology; Humans; Phenols/pharmacology; Phenols/therapeutic use; Prolactin/metabolism*; Prolactin/pharmacology; Receptors, Estrogen/metabolism; Receptors, Prolactin/metabolism