Regulation of development of the normal mammary gland by hormones and growth factors

Vonderhaar, Barbara K.

doi:10.1007/978-1-4613-1733-3_12

Cited by 68 publications

(34 citation statements)

References 51 publications

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“…In the mouse, these hormones produce some development with each estrous cycle, and massive development at pregnancy that never fully regresses after estrus or weaning, resulting in ever-increasing alveolar and ductal development with each episode (Vonderhaar 1988). As prolactin has long been known to be essential for mammary gland development, lactational problems were expected in females carrying a null mutation of the PRLR gene.…”

Section: Mammary Gland Development and Lactationmentioning

confidence: 99%

Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse.

Ormandy¹,

Camus²,

Barra³

et al. 1997

Genes Dev.

722

429

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Mice carrying a germ-line null mutation of the prolactin receptor gene have been produced by gene targeting in embryonic stem cells. Heterozygous females showed almost complete failure of lactation attributable to greatly reduced mammary gland development after their first, but not subsequent, pregnancies. Homozygous females were sterile owing to a complete failure of embryonic implantation. Moreover, they presented multiple reproductive abnormalities, including irregular cycles, reduced fertilization rates, defective preimplantation embryonic development, and lack of pseudopregnancy. Half of the homozygous males were infertile or showed reduced fertility. This work establishes the prolactin receptor as a key regulator of mammalian reproduction, and provides the first total ablation model to further study the role of the prolactin receptor and its ligands.

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Section: Mammary Gland Development and Lactationmentioning

confidence: 99%

Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse.

Ormandy¹,

Camus²,

Barra³

et al. 1997

Genes Dev.

722

429

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“…The addition of progesterone to this regimen causes side branching, while alveolar development resembling that of pregnancy requires the addition of prolactin . These hormone combinations were shown to produce similar results using serum-free in vitro culture of whole mammary glands, although mammary development did not achieve the extent seen in vivo (Ichinose and Nandi, 1964;Vonderhaar, 1988), suggesting that indirect systemic effects of these hormones are important for full development. …”

Section: Introductionmentioning

confidence: 94%

“…In utero, a rudimentary ductal structure is produced. During puberty the resulting ducts elongate and bifurcate to fill the mammary fat pad, and ductal side branching and the formation of alveolar buds occur during each estrous cycle (Vonderhaar, 1988). During pregnancy, the alveolar buds give rise to lobuloalveolar structures capable of milk production.…”

mentioning

confidence: 99%

Control of the Mammary Cell Cycle Clock By Estrogen and Progesterone

Weinberg¹

1997

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget,. Washington, DC 20503 AGENCY USE ONLY (Leave blank)2. REPORT DATE January 2 001 REPORT TYPE AND DATES COVEREDFinal (15 Jul 96 -31 Dec 00) TITLE AND SUBTITLE Control of the Mammary Cell Cycle Clock by Estrogen and Progesterone AUTHOR(S)Robert A. Weinberg, Ph.D. Both the growth and the development of the mammary gland are controlled by the female hormones estrogen, prolactin and progesterone, and by interactions between the epithelial and stromal compartments of the breast. Changes in the regulation of any of these processes may lead to breast cancer. We have investigated the role of progesterone in the process of sidebranching and alveologenesis in the mammary gland using mice lacking the progesterone receptor which are defective in these processes. By reconstituting murine mammary glands in vivo, we have shown that the progesterone receptor is required only in epithelial cells for proper sidebranching and alveologenesis to occur. Our studies indicate that progesterone acts in a paracrine manner and suggest that Wnt-4 is a mediator of the paracrine signals released from progesterone receptor-positive cells. In addition, we have characterized the role of the estrogen receptor (ER) in regulating the proliferation of breast cancer cells. We postulate that the ability of ER to control cyclin Dl expression and proliferation of breast cancer cells may be acquired during breast cancer progression. This is indicated by the fact that ectopic expression of the estrogen receptor in human epithelial cells does not, on its own, enable signaling between the ER and the cyclin Dl gene. Moreover, others have demonstrated that the ER-positive cells in the mammary epithelium are distinguishable from those that are actively mitotic. Finally, our work indicates that the effects of deletion of the prolactin receptor (PrlR) from mammary epithelial cells closely phenocopy the consequences of deleting cyclin Dl from these cells. We suggest that activation of the PrlR by its ligand results in the production of jnsuliJl-like growth factor-2 which in turn induces cyclin Dl synthesis in these cells^ ; - Conclusions 8 FUNDING NUMBERS DAMD17-96-1-6285 PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)Whitehead SUBJECT TERMS Breast CancerReferences 9Appendices 10Final Report Laboratory of Robert A. Weinberg Ph.D.DAMD 17-96-1-6285Our research performed under the auspices of the Army Breast Cancer grant has focused on the ab...

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“…1,5 Both EGF and transforming growth factor-a (TGF-a) can stimulate the proliferation of mammary epithelial cells and lobulo-alveolar development in the mammary gland of virgin mice. 1,6 These growth factors are also able to modulate milk protein expression in mammary epithelial cells when cells are exposed to lactogenic hormones 7 and can inhibit apoptosis in secretory alveolar epithelial cells in the involuting mammary gland when ectopically overexpressed. 8 We recently identified another EGF-related protein, CR-1 (cripto-1) that can also modulate mammary epithelial cell morphogenesis and differentiation.…”

Section: Introductionmentioning

confidence: 99%

Cripto-1 induces apoptosis in HC-11 mouse mammary epithelial cells

Santis

Martínez-Lacaci²,

Bianco³

et al. 2000

Cell Death Differ

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Cripto-1 (CR-1) is an epidermal growth factor (EGF)-related protein. CR-1 can inhibit b-casein and whey acidic protein expression in mouse mammary epithelial cells. The present study demonstrates that CR-1 can induce apoptosis in HC-11 mouse mammary epithelial cells, as measured by bisbenzimide stained nuclei, TUNEL assay and cell death ELISA. Apoptosis could be observed after 2 days of exposure of confluent HC-11 cells to CR-1 in the absence of the survival factors EGF and insulin, with maximum apoptosis occurring at 3 days. A reduction in poly(ADP-ribose) polymerase (PARP) expression and an increase in b-catenin cleavage was found after 18 h of exposure to CR-1 suggesting that apoptosis was preceded by the induction of a caspase activity since the caspase inhibitor ZFAD.FMK could block the CR-1-induced reduction in PARP expression and CR-1-induced apoptosis. CR-1 was found to increase the expression of caspase-3-like protease. Although, the levels of p27 kip1 and p21Bax did not change after exposure to CR-1 for 18 h, the levels of Bcl-x L became undetectable. These studies suggest that CR-1 promotes apoptosis by mediating the induction of caspase-3-like protease and downregulating the expression of Bcl-x L .

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Regulation of development of the normal mammary gland by hormones and growth factors

Cited by 68 publications

References 51 publications

Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse.

Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse.

Control of the Mammary Cell Cycle Clock By Estrogen and Progesterone

Cripto-1 induces apoptosis in HC-11 mouse mammary epithelial cells

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