Hormonal Regulation of Mammary Tumors, 1982 Volume II: Peptide and Other Hormones

The concept that hormones influence tumor growth originated in 1889 with the proposal of Albert Schinzinger who suggested that breast cancer is related to the ovaries. Several years later, Sir George Beatson observed that remission of disseminated breast cancer could be achieved in premenopausal patients by performing bilateral oophorectomy. As a result of the contri­ butions of Hedley Atkins, Charles Huggins and others, additive and ablative hormonal therapies have been widely used for the treatment of advanced breast cancers for several decades. Model systems to study the effects of hormones on growth and regression of breast tumors have been available for many years; however, the complexities of the hormonal environment have rendered in vivo studies difficult in man and experimental animals. Recently, the availability of long-term cultures of breast cancer cells has stimulated many investigators to use these cell lines to unravel the mechanisms of hormone action. Because of the extreme diversity and complexity of advances regarding the endocrinology of the breast and breast cancers, a multi-authored review was deemed necessary. It has been gratifying to receive contributions from many noted scholars. In Volume I of this monograph, the influence of steroid hormones and their antagonists upon normal and neoplastic tissues of the mammary gland are presented. In Volume II, the effects of peptide and other hormones are reviewed.

1 Role of Prolactin or Placental Lactogen in Mammary Tumor Development in Experimental Animals.- Prolactin or placental lactogen and mammary tumor development.- Promotion by prolactin of mammary tumor development.- Promotion by prolactin of preneoplastic mammary gland lesions.- Promotion by placental lactogen of preneoplastic and neoplastic mammary gland development.- Difference in susceptibility to prolactin or placental lactogen between normal and neoplastic mammary glands.- Inhibition by prolactin of mammary tumor development.- A mechanism of role of prolactin in mammary tumor development.- Stimulation by prolactin of mammary gland DNA synthesis, a primary factor for mammary tumor development.- Synergism of prolactin and estrogen in mammary gland DNA synthesis.- Species-difference in mammary gland DNA synthesis in response to prolactin.- Factors which modulate mammary tumor development and prolactin secretion.- Perinatal hormonal exposure.- Dietary fat.- Immunopotentiation.- Role of prolactin in mammary tumor virus production.- Strain-difference in circulating levels of prolactin or placental lactogen and mammary gland susceptibility to it.- Strain-difference in hormone levels.- Strain-difference in mammary gland susceptibility to prolactin in mice.- Future prospects.- References.- 2 Prolactin and Prolactin Receptors in Tumor Development, Growth and Cellular Functions.- Models of hormone-dependent mammary cancer.- Mice.- Rats.- In vitro systems.- Hormonal regulation of PRL receptors in normal tissue.- Measurement of prolactin receptors.- Receptor levels during pregnancy and lactation.- Up-regulation.- Down-regulation.- Hormonal regulation of receptors in mammary tumors.- DMBA-induced mammary tumors.- Regression of DMBA-induced tumors by RU16117.- NMU-induced mammary tumors.- Organ culture of mammary tumors.- Prolactin and human breast cancer.- Evidence for role of prolactin.- Prolactin receptors in human breast carcinoma.- Summary and conclusions.- References.- 3 Studies of Prolactin Receptors and the Possible Proliferative Role of Prolactin and Other Pituitary Factors in Human Breast Tumor Cells.- References.- Acknowledgement.- 4 Mode of Action of Prolactin on Normal and Neoplastic Mammary Tissues.- Prolactin receptors.- Internalization of prolactin.- Actions of prolactin at the plasma membrane.- Sodium-potassium hypothesis.- Calcium ions.- Polyamines, prostaglandins and cyclic nucleotides.- Phospholipase A2.- Prostaglandins (PG).- Cyclic nucleotides.- Polyamines.- Actions of prolactin on the proliferation of mammary cells.- References.- 5 Growth Factors for Hormone-Sensitive Tumor Cells.- Effects of known growth factors on mammary tumor cell proliferation.- Hormonally defined media.- Growth factor effects on cells cultured in collagen supported matrices.- Effects of other growth factors on mammary origin cells.- Effects of estrogens on growth factor activities for estrogen-responsive tumor cells.- New approaches to estrogen-responsive tumor growth.- Endocrine estromedin mechanism.- Paracrine and/or autocrine estromedin growth stimulation.- Platelet derived growth factors.- Platelet derived growth factors for mammary tumor cells.- Growth factors and growth control in normal versus malignant mammary cells.- Pituitary derived mammary cell growth factors.- Summary of new approaches to growth factor involvement in mammary tumor growth in vivo.- References.- 6 Primary and Permissive Actions of Insulin in Breast Cancer.- I. Direct actions of insulin on experimental mammary tumors.- A. Stimulation of growth: insulin-dependent tumors.- B. Inhibition of growth: insulin-responsive tumors.- C. Actions of insulin and relationship to tumor growth.- II. Facilitative effects of insulin on mammary tumors.- III. Estrogen-insulin interactions.- IV. Insulin and human breast cancer.- V. Conclusions.- Acknowledgement.- References.- 7 Effect of Thyroid Hormones on Mammary Tumor Induction and Growth.- Epidemiologic and clinical studies.- Animal studies.- Mammary tumorigenesis.- Normal mammary gland development.- Possible mechanisms.- References.- 8 Mode of Cyclic Amp Action in Growth Control.- Normal and neoplastic growth of the mammary gland.- Intracellular content of cyclic nucleotides.- Hormone-cyclic nucleotide interrelation.- Mechanism of mammary tumor regression.- Exogenous cyclic nucleotides.- Cyclic AMP receptor proteins.- Antagonism between cyclic AMP and estrogen.- Nuclear protein phosphorylation.- Cyclic nucleotides in transformation.- Cyclic AMP in reversion of malignancy.- Conclusion.- Acknowledgement.- References.- 9 Prostaglandins, Fatty Acids and Phospholipids in Normal and Neoplastic Breast Tissues.- Content of fatty acids and phospholipids.- Normal mammary tissues.- Mammary tumors.- Metabolism of phospholipids.- Normal mammary gland.- Mammary tumors.- Effects of dietary lipids.- Mammary tumorigenesis and growth.- Effect on tumor lipids.- Effects of dietary carbohydrates.- Lipid inducers of cell transformation.- Fatty acid synthesis.- Phospholipases and prostaglandins.- Mammary gland lipids in response to hormonal regulation.- Acknowledgement.- References.- 10 Polyamines in Normal and Neoplastic Growth of Mammary Gland.- Developmental changes in the synthesis and accumulation of polyamines in mammary gland.- The control of polyamine biosynthesis during cell proliferation of mammary gland in vitro.- The control of polyamine biosynthesis during differentiation in vitro.- The functions of polyamines during mammary cell proliferation.- Spermidine.- Putrescine.- The role of polyamines in the differentiation of mammary gland.- Milk protein synthesis.- Spermidine and glucocorticoid action.- The effect of spermidine on cellular components.- Differential actions of glucocorticoid and spermidine.- Spermidine and cell-free translation of mammary mRNAs.- Polyamine transport.- Concluding remark.- References.- 11 Hormone Regulation of Casein Gene Expression in Normal and Neoplastic Cells in Murine Mammary Glands.- I. Introduction.- II. General macromolecular activity.- III. Direct measure of casein mRNA.- A. Specific translation activity.- B. Hormonal regulation of mRNAcsn translational activity.- IV. Purification of casein mRNA and synthesis of complementary DNA.- V. Quantitative measurement of casein gene expression by the cDNAcsn.- A. Adrenal glucocorticoid influence on casein mRNA accumulation in mammary gland in vivo.- B. Measurement of specific casein mRNA transcription.- C. Measurement of casein gene transcription.- VI. Hormonal modulation of casein gene transcription.- VII. Casein gene expression in mammary tissue in vitro.- A. Organ culture of pieces of mammary tissue from pregnant animals.- B. The whole mammary organ in culture.- VIII. Casein gene expression in a two-step culture model of the whole mammary organ.- A. Measured by translational assay.- B. Measured by molecular hybridization with cDNAcsn probe.- IX. Simultaneous occurrence of morphogenesis and casein gene expression.- X. Glucocorticoid is obligatory to casein gene expression.- XI. Negative influence of progesterone on casein gene expression.- XII. Cloning of cDNAcsn.- XIII. Mammary neoplasia and casein gene expression.- A. In mammary cells transformed in vivo.- B. In mammary cells transformed in vitro.- XIV. Summary and comments.- Acknowledgements.- References.