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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

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Päivi Järvensivu, Taija Heinosalo, Janne Hakkarainen, Pauliina Kronqvist, Niina Saarinen and Matti Poutanen

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

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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

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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.

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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.

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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.

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H A Hahm and N E Davidson

Apoptosis or Programmed Cell Death (PCD) is an active, energy dependent process of cell death which occurs during development, in response to certain physiologic stimuli, and secondary to cell injury and stress (reviewed by Wyllie 1980, Arends and Wyllie 1991, Ellis et al. 1991,Wyllie 1992). This type of cell death occurs via controlled deletion of discrete cells within a tissue and plays a role in embryonic development and normal tissue homeostasis. It differs from necrotic cell death in that the cells eliminated by PCD die and are processed without initiation of an inflammatory response.

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Yuet-Kin Leung, Vinothini Govindarajah, Ana Cheong, Jennifer Veevers, Dan Song, Robin Gear, Xuegong Zhu, Jun Ying, Ady Kendler, Mario Medvedovic, Scott Belcher and Shuk-Mei Ho

proved critical to assess the effects of single and/or multiple exposures on susceptible windows of mammary gland development and in the subsequent identification of factors relevant for breast cancer prevention in humans. The mammary gland has been

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Ofelia Soriano, Guadalupe Delgado, Brenda Anguiano, Pavel Petrosyan, Edith D Molina-Servín, Maria E Gonsebatt and Carmen Aceves

Introduction A robust body of information supports the notion that moderately high concentrations of iodine may reduce pathologies in several iodine-uptake tissues such as thyroid, mammary gland, intestine, and prostate ( Venturi et al . 2000

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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