Introduction Postpubertal mammary gland development is extensively hormonally regulated, and 17-beta-estradiol (E2) is a hormone essential for normal postpubertal mammary gland development. In hormone-deprived mice, additive and sequential
Päivi Järvensivu, Taija Heinosalo, Janne Hakkarainen, Pauliina Kronqvist, Niina Saarinen and Matti Poutanen
Hema Parmar and Gerald R Cunha
Introduction The mammary gland is a useful model in which to study epithelial–stromal interactions, as these interactions are important in embryonic development, postnatal ductal growth, ductal branching morphogenesis and
Allison Sumis, Katherine L Cook, Fabia O Andrade, Rong Hu, Emma Kidney, Xiyuan Zhang, Dominic Kim, Elissa Carney, Nguyen Nguyen, Wei Yu, Kerrie B Bouker, Idalia Cruz, Robert Clarke and Leena Hilakivi-Clarke
-OID: 15. Tissue collection after tumor monitoring period Blood was obtained via cardiac puncture at killing. Serum was separated, frozen and kept at −20°C until assayed. Mammary glands and tumors were collected at killing. Tissues were either fixed
R Kumar, R K Vadlamudi and L Adam
Homeostasis in normal tissue is regulated by a balance between proliferative activity and cell loss by apoptosis. Apoptosis is a physiological mechanism of cell loss that depends on both pre-existing proteins and de novo protein synthesis, and the process of apoptosis is integral to normal mammary gland development and in many diseases, including breast cancer. The mammary gland is one of the few organ systems in mammals that completes its morphologic development postnatally during two discrete physiologic states, puberty and pregnancy. The susceptibility of the mammary gland to tumorigenesis is influenced by its normal development, particularly during stages of puberty and pregnancy that are characterized by marked alterations in breast cell proliferation and differentiation. Numerous epidemiologic studies have suggested that specific details in the development of the mammary gland play a critical role in breast cancer risk. Mammary gland development is characterized by dynamic changes in the expression profiles of Bcl-2 family members. The expression of Bcl-2 family proteins in breast cancer is also influenced by estradiol and by progestin. Since the ratio of proapoptotic to antiapoptotic proteins determines apoptosis or cell survival, hormone levels may have important implications in the therapeutic prevention of breast cancer.
B Spencer-Dene, C Dillon, V Fantl, K Kerr, A Petiot and C Dickson
Fibroblast growth factors (Fgfs) and their receptors are important intercellular signalling molecules involved in many aspects of animal development. The aberrant expression of the Fgfs or the inappropriate activation of their cell surface receptors have been implicated in tumorigenesis. Here, we describe the evidence that as well as playing a critical role in the formation of the mammary primordia during embryogenesis, signalling by Fgfs is necessary for optimal lobuloalveolar development of the mouse mammary gland during pregnancy.
Amulya Sreekumar, Kevin Roarty and Jeffrey M Rosen
Introduction The mammary gland distinguishes itself from other organs since much of its development occurs after birth, allowing for adult developmental studies. Postnatal development of the mammary gland comprises stages of ductal morphogenesis
Bruno M Simões, Denis G Alferez, Sacha J Howell and Robert B Clarke
, Harrison et al . 2013 , Simões et al . 2015 ). Similar to what happens in the normal mammary gland, it has been suggested that estrogen can promote CSC activity of ER − BCSCs by inducing the secretion of paracrine growth factors from ER + cells
Gerard A Tarulli, Lisa M Butler, Wayne D Tilley and Theresa E Hickey
Introduction Development of the adult mammary gland and its function are dependent upon oestrogen and progesterone acting via the oestrogen receptor alpha (ERa (ESR1)) and progesterone receptor (PR (PGR)) respectively. During reproductive cycles
R R Tekmal, N Kirma, K Gill and K Fowler
To test directly the role of breast-tissue estrogen in initiation of breast cancer, we have developed the aromatase-transgenic mouse model and demonstrated for the first time that increased mammary estrogens resulting from the overexpression of aromatase in mammary glands lead to the induction of various preneoplastic and neoplastic changes that are similar to early breast cancer. Continued overexpression of aromatase that leads to increased breast-tissue estrogen contributes to a number of epigenetic changes in mammary tissue such as alteration in the regulation of genes involved in apoptosis, activation of genes involved in cell cycle and cell proliferation, and activation of a number of growth factors. Our current studies show aromatase overexpression is sufficient to induce and maintain early preneoplastic and neoplastic changes in female mice without circulating ovarian estrogen. Preneoplastic and neoplastic changes induced in mammary glands as a result of aromatase overexpression can be completely abrogated with the administration of the aromatase inhibitor, letrozole. Consistent with complete reduction in hyperplasia, we have also seen downregulation of estrogen receptor and a decrease in cell proliferation markers, suggesting aromatase-induced hyperplasia can be treated with aromatase inhibitors. Our studies demonstrate that aromatase overexpression alone, without circulating estrogen, is responsible for the induction of breast hyperplasia and these changes can be abrogated using aromatase inhibitors.
Vasily N Aushev, Kalpana Gopalakrishnan, Susan L Teitelbaum, Humberto Parada Jr, Regina M Santella, Marilie D Gammon and Jia Chen
development induced changes in histology and development of mammary glands ( Manservisi et al. 2015 ) and further identified a gene signature of exposure to low-dose DEP and MPB in the rat mammary glands: a set of genes was shown to be differentially