The Normal Development of the Mammary Glands of Virgin Female Mice of Ten Strains Varying in Susceptibility to Spontaneous Neoplasms

Gardner, W. U.; Strong, Leonell C.

doi:10.1158/ajc.1935.282a

Cited by 42 publications

(14 citation statements)

References 2 publications

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“…Although inbred strain comparisons of mammary gland development have been made by others (Gardner and Strong 1935; Gibson 1930; Huseby and Bittner 1946; Naylor and Ormandy 2002; Olson et al 2010; Yant 1998), the 17 different strains described in all of these studies combined is still small in comparison to the roughly 224 inbred strains described in the mouse phenome database (http://phenome.jax.org/). Of these 17 “classical” strains, 7 were available and included in the current work.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In this regard, early studies on select inbred mouse strains demonstrated a link between the extent of ductal development and later development of mammary tumors (Apolant 1906; Gardner and Strong 1935; Gibson 1930; Haaland 1911). These studies also found that certain strains exhibited altered mammary gland number and placement and displayed estrus-cycle-dependent variation in ductal morphology (Gardner and Strong 1935). This work ultimately led to the conclusion that mammary ductal development was controlled by three factors; 1) the hormonal stimulation to which the mammae were subject, 2) the presence of an agent transmitted through the milk which was later identified as mouse mammary tumor virus (MMTV), and 3) the genetic constitution of the animal (Huseby and Bittner 1946).…”

Section: Introductionmentioning

confidence: 99%

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In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

Hadsell

Olea

et al. 2015

Mamm Genome

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Genetic background plays a dominant role in mammary gland development and breast cancer (BrCa). Despite this, the role of genetic diversity in mammary gland development is only partially understood. This study used strain-dependent variation in an inbred mouse mapping panel, to identify quantitative trait loci (QTL) underlying structural variation in mammary ductal development, and determined if these QTL correlated with genomic intervals conferring breast cancer susceptibility in humans. For about half of the traits, the observed variation among the complete set of strains in this study was greater (P<0.05) than that observed with previously studied strains or with strains that are in current common use for mammary gland biology. Correlations were also detected with previously reported variation in mammary tumor latency and metastasis. In silico genome-wide association (GWAS) identified 20 mammary development QTL (Mdq). Of these, 5 were syntenic with previously reported human BrCa loci. The most highly significant (P=1×10 −11 ) association of the study was on MMU6 and contained the genes Plxna4, Plxna4os1, and Chchd3. On MMU5, a QTL was detected (p=8×10 −7 ) that was syntenic to a human BrCa locus on h12q24.5 containing the genes Tbx3 and Tbx5. Intersection of highassociation SNP (r 2 >0.8) with genomic and epigenomic features, and intersection of candidate genes with gene expression and survival data from human BrCa highlighted several for further study. These results support the conclusion that genetic variation in mammary ductal development is greater than previously appreciated. They also suggest that mammary tumor latency and metastatic index may be influenced by variations in the same factors that control normal mammary ductal development and that further studies of genetically diverse mice can improve our understanding of the connection between breast development and breast cancer in humans by identifying novel susceptibility genes. HHS Public Access

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

Hadsell

Olea

et al. 2015

Mamm Genome

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“…In mice, strains with robust lateral branching in the ductal tree show high incidence of spontaneous mammary tumors (3)(4)(5). Moreover, the specific location where a tumor develops in the breast can have a profound effect on the resulting breast cancer outcome: patients with tumors in the upper lateral quadrant of the breast have a better prognosis than those with tumors that develop in one of the other three quadrants (6,7).…”

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confidence: 99%

Host epithelial geometry regulates breast cancer cell invasiveness

Boghaert¹,

Gleghorn²,

Lee

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Breast tumor development is regulated in part by cues from the local microenvironment, including interactions with neighboring nontumor cells as well as the ECM. Studies using homogeneous populations of breast cancer cell lines cultured in 3D ECM have shown that increased ECM stiffness stimulates tumor cell invasion. However, at early stages of breast cancer development, malignant cells are surrounded by normal epithelial cells, which have been shown to exert a tumor-suppressive effect on cocultured cancer cells. Here we explored how the biophysical characteristics of the host microenvironment affect the proliferative and invasive tumor phenotype of the earliest stages of tumor development, by using a 3D microfabrication-based approach to engineer ducts composed of normal mammary epithelial cells that contained a single tumor cell. We found that the phenotype of the tumor cell was dictated by its position in the duct: proliferation and invasion were enhanced at the ends and blocked when the tumor cell was located elsewhere within the tissue. Regions of invasion correlated with high endogenous mechanical stress, as shown by finite element modeling and bead displacement experiments, and modulating the contractility of the host epithelium controlled the subsequent invasion of tumor cells. Combining microcomputed tomographic analysis with finite element modeling suggested that predicted regions of high mechanical stress correspond to regions of tumor formation in vivo. This work suggests that the mechanical tone of nontumorigenic host epithelium directs the phenotype of tumor cells and provides additional insight into the instructive role of the mechanical tumor microenvironment.host-tumor interactions | mechanotransduction | focal adhesion kinase | integrin clustering

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“…In 1938, Fekete (Fekete 1938) described areas of hyperplasia that appeared to directly progress to mammary cancer. In the same year, Gardner (Gardner et al 1939) described different forms of hyperplastic lesions that involved either the ductal component or the alveolar component of the mammary tree and suggested that these lesions progressed to mammary cancers. A large number of investigators in the 1940s and 1950s provided similar and additional observations on the pathobiology of mammary cancer and emphasized the significance of these hyperplastic lesions in the development of mammary cancer (reviewed in Medina 1973a).…”

Section: The Very Beginningmentioning

confidence: 99%

Of Mice and Women: A Short History of Mouse Mammary Cancer Research with an Emphasis on the Paradigms Inspired by the Transplantation Method

Medina¹

2010

Cold Spring Harbor Perspectives in Biology

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The ability to transplant mammary epithelial cells of any age or developmental stage to the normal anatomical site of an inbred recipient mouse strain has revolutionized the studies of mammary development and tumor biology over the past 50 years. This simple method has made the mammary gland of the rodent one of the most accessible and studied organs and facilitated our understanding of the fundamental cellular and molecular properties of normal and neoplastic development. This short review outlines the early concepts that led to the development of the transplantation technology and the impact of this method on our understanding for a variety of processes important both for the normal development and differentiation of the gland as well as the phenomena of neoplastic progression.

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The Normal Development of the Mammary Glands of Virgin Female Mice of Ten Strains Varying in Susceptibility to Spontaneous Neoplasms

Cited by 42 publications

References 2 publications

In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

Host epithelial geometry regulates breast cancer cell invasiveness

Of Mice and Women: A Short History of Mouse Mammary Cancer Research with an Emphasis on the Paradigms Inspired by the Transplantation Method

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