Abstract:
:With improved screening methods, the numbers of abnormal breast lesions diagnosed in women have been increasing over time. However, it remains unclear whether these breast lesions will develop into invasive cancers. To more effectively predict the outcome of breast lesions and determine a more appropriate course of treatment, it is important to understand the underlying mechanisms that regulate progression of non-invasive lesions to invasive breast cancers. A hallmark of invasive breast cancers is the accumulation of fibroblasts. Fibroblast proliferation and activation in the mammary gland is in part regulated by the Transforming Growth Factor beta1 pathway (TGF-β). In animal models, TGF-β suppression of CCL2 and CXCL1 chemokine expression is associated with metastatic progression of mammary carcinomas. Here, we show that transgenic overexpression of the Polyoma middle T viral antigen in the mouse mammary gland of C57BL/6 mice results in slow growing non-invasive lesions that progress to invasive carcinomas in a stage dependent manner. Invasive carcinomas are associated with accumulation of fibroblasts that show decreased TGF-β expression and high levels of CXCL1, but not CCL2. Using co-transplant models, we show that decreased TGF-β signaling in fibroblasts contribute to mammary carcinoma progression through enhancement of CXCL1/CXCR2 dependent mechanisms. Using cell culture models, we show that CXCL1 mediated mammary carcinoma cell invasion through NF-κB, AKT, Stat3 and p42/44MAPK dependent mechanisms. These studies provide novel mechanistic insight into the progression of pre-invasive lesions and identify new stromal biomarkers, with important prognostic implications.
journal_name
J Mammary Gland Biol Neoplasiajournal_title
Journal of mammary gland biology and neoplasiaauthors
Bernard S,Myers M,Fang WB,Zinda B,Smart C,Lambert D,Zou A,Fan F,Cheng Ndoi
10.1007/s10911-018-9407-1subject
Has Abstractpub_date
2018-12-01 00:00:00pages
249-267issue
4eissn
1083-3021issn
1573-7039pii
10.1007/s10911-018-9407-1journal_volume
23pub_type
杂志文章abstract::Mammalian cells depend on phospholipid (PL) and fatty acid (FA) transport to maintain membrane structure and organization, and to fuel and regulate cellular functions. In mammary glands of lactating animals, copious milk secretion, including large quantities of lipid in some species, requires adaptation and integratio...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-014-9318-8
更新日期:2014-03-01 00:00:00
abstract::During normal mammary gland development, the tyrosine kinase Jak2 and its main substrate, the signal transducer and activator of transcription-5 (Stat5), are critical for the growth and differentiation of alveolar progenitors as well as the survival of secretory mammary epithelial cells. Genetic studies in mouse model...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-008-9062-z
更新日期:2008-03-01 00:00:00
abstract::With the discovery of an activated Notch oncogene as a causative agent in mouse mammary tumor virus induced breast cancer in mice, the potential role for Notch signaling in normal and pathological mammary development was revealed. Subsequently, Notch receptors have been found to regulate normal development in many org...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/B:JOMG.0000037159.63644.81
更新日期:2004-04-01 00:00:00
abstract::The mouse has emerged as a primary animal model for human breast cancer because the mammary glands of the two species are very similar in structure and function. In this regard the TDLU and LA have similar morphology. The mouse, infected by MMTV, develops "spontaneous" tumors with specific but limited tumor phenotypes...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1018712905244
更新日期:1999-01-01 00:00:00
abstract::The microenvironment of a tumor has emerged recently as a critical contributor to the development of cancer. Within this environment, fibroblasts and immune cells are the cell lineages that seem to be active mediators of tumour development. The activated fibroblasts that are also present during wound healing and chron...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-014-9326-8
更新日期:2014-07-01 00:00:00
abstract::Mammary gland involution is a period of intensive tissue remodeling. Over the course of a relatively brief period, a large proportion of the mammary gland epithelium undergoes programmed cell death and is removed by phagocytes. In addition, the gland is cleared of residual milk fat globules as well as milk and adipocy...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-007-9036-6
更新日期:2007-03-01 00:00:00
abstract::The Notch receptor protein and its signaling pathway have been well conserved throughout evolution and appear to be pivotal components in cell fate decisions during development. Recent studies suggest that, depending on the cellular and developmental context, Notch signaling may also affect cell proliferation and prog...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1009512414430
更新日期:2001-01-01 00:00:00
abstract::Premalignant breast disease in humans is a concept that admits to a broad range of elements and possible determinants predicting the likelihood of developing breast cancer. Most of these elements are relative, such as the risk of breast cancer for women that is 130 times that of men and peaks at a younger age by about...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1009521726605
更新日期:2000-10-01 00:00:00
abstract::It has long been appreciated that the estrogen receptor (ER) plays an important role in the biology of breast cancer. It is an accepted factor predicting favorable disease outcome and treatment response, and as such is generally considered to represent a "good" prognostic marker in breast cancer. In this review we pre...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1014782813943
更新日期:2001-10-01 00:00:00
abstract::Insulin-like growth factor-I and -II (IGF-I and IGF-II) and/or the type I insulin-like growth factor receptor (IGF-IR) have been implicated in a number of human tumors including breast cancer. However, despite being implicated in breast cancer for approximately 25 years and given that transgenic technology has been av...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-008-9097-1
更新日期:2008-12-01 00:00:00
abstract::Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conformation initiated ...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-010-9170-4
更新日期:2010-03-01 00:00:00
abstract::Localised breast cancer can be cured by surgery and adjuvant treatments, but mortality remains high as some tumours metastasize early. Perlecan is a basement membrane (BM) protein involved in tumour development and progression. Here, mRNA and protein expression of perlecan, and mRNA expression of matrix degrading enzy...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章
doi:10.1007/s10911-020-09447-2
更新日期:2020-03-01 00:00:00
abstract::Transgenic experiments using oocyte micro-injection methodology are often performed in order to target expression of a foreign gene in a specific tissue or, to a lesser extent, to study the regulation of gene expression. However, the isolation of embryonic stem cells in mice and the development of antisense and ribozy...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1018775729834
更新日期:1998-07-01 00:00:00
abstract::Much of our knowledge about the intricate pathways and molecular mechanisms involved in the conversion of a normal mammary epithelial cell to malignancy derives from studies on mammary tumorigenesis induced by the retrovirus mouse mammary tumor virus. In addition, three DNA tumor viruses, simian virus 40, polyomavirus...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/BF02096302
更新日期:1996-01-01 00:00:00
abstract::The development and progression of aggressive breast cancer is characterized by genomic instability leading to multiple genetic defects, phenotypic diversity, chemoresistance, and poor outcome. Centrosome abnormalities have been implicated in the origin of chromosomal instability through the development of multipolar ...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/B:JOMG.0000048774.27697.30
更新日期:2004-07-01 00:00:00
abstract::The ability to produce and expel milk is important for the health and survival of all mammals. Nevertheless, our understanding of the molecular events underlying the execution of this process remains incomplete. Whilst impaired mammary gland development and lactational competence remains the subject of focused investi...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-020-09467-y
更新日期:2020-11-19 00:00:00
abstract::Inflammation of the adipose tissues occurs in association with obesity. This inflammatory process leads to the induction of cyclooxygenase-2 (COX-2) expression and a consequent elevation in prostaglandin (PG) production, which, together with proinflammatory cytokines, induce aromatase expression and estrogen synthesis...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-013-9299-z
更新日期:2013-12-01 00:00:00
abstract::The Hedgehog pathway is critical for many developmental processes, including the formation of several epidermal appendages. In the mammary gland strict regulation of the Hedgehog pathway is required for normal development. Alterations in Hedgehog signaling result in defects in both the embryonic and postnatal mammary ...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-007-9048-2
更新日期:2007-09-01 00:00:00
abstract::The neuroendocrine hormone prolactin (PRL) stimulates breast growth and differentiation during puberty, pregnancy, and lactation. Despite extensive and convincing data indicating that PRL significantly contributes to the pathogenesis and progression of rodent mammary carcinoma, parallel observations for human breast c...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1026325630359
更新日期:1997-01-01 00:00:00
abstract::Breast cancer is a heterogeneous disease comprised of at least five major tumor subtypes that coalesce as the second leading cause of cancer death in women in the United States. Although metastasis clearly represents the most lethal characteristic of breast cancer, our understanding of the molecular mechanisms that go...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-011-9207-3
更新日期:2011-06-01 00:00:00
abstract::Human mammary epithelial cells emerge spontaneously from senescence, exhibiting eroding telomeric sequences, and ultimately enter crisis to generate the type of chromosomal abnormalities seen in early stages of breast cancer. In a mouse mammary tumor model, the spontaneous escape of senescence can be observed as an in...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/B:JOMG.0000023590.63974.f8
更新日期:2004-01-01 00:00:00
abstract::The differentiation and function of mammary epithelial cells is dependent upon the combined action of growth factor/hormone receptors and integrin receptors, which act in concert to control the signals required for normal cell function. It is now becoming clear that integrin receptors also contribute to carcinoma cell...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1018766317055
更新日期:1999-10-01 00:00:00
abstract::Analysis of genes and proteins involved in lipid biosynthesis in mammary epithelial cells (MECs) is complicated by the presence of adipose tissue in the mammary gland, which may be predominant in whole tissue lysates depending upon developmental stage. We have developed a method based on protocols used to establish pr...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章
doi:10.1007/s10911-009-9161-5
更新日期:2009-12-01 00:00:00
abstract::Ductal development in the pubertal mouse mammary gland is characterized by dramatic morphological changes in the epithelium driven by proliferation of cap and body cells in the terminal endbuds. Recent experiments revealed a coincident and abundant apoptosis in the body cells of these structures. The cells undergoing ...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1018733426625
更新日期:1999-04-01 00:00:00
abstract::Milk is primarily regarded as a food furnishing essential nutrients for infant growth and development, but milk can also serve as a vehicle for mother to neonate transfer of molecules that regulate development. A wide array of biologically active compounds such as hormones, cytokines and enzymes are present in milk, e...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/BF02018079
更新日期:1996-07-01 00:00:00
abstract::The ErbB receptor tyrosine kinase family has often been associated with increased growth of breast epithelial cells, as well as malignant transformation and progression. In contrast, ErbB4/HER4 exhibits unique attributes from a two step proteolytic cleavage which releases an 80 kilodalton, nuclear localizing, tyrosine...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-008-9080-x
更新日期:2008-06-01 00:00:00
abstract::T cell immunity in breast cancer is suggested to play a role in tumor dormancy, a period of stability which can correspond to the time interval between primary treatment and tumor recurrence. Bone marrow in breast cancer patients seems to be particularly important because it is highly enriched with cancer specific mem...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1020308104613
更新日期:2002-04-01 00:00:00
abstract::We review the role of Neuregulin 3 (Nrg3) and Erbb receptor signalling in embryonic mammary gland development. Neuregulins are growth factors that bind and activate its cognate Erbb receptor tyrosine kinases, which form a signalling network with established roles in breast development and breast cancer. Studies have s...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-013-9286-4
更新日期:2013-06-01 00:00:00
abstract::Dynamic interactions between the hormone responsive mammary gland epithelium and surrounding stromal macrophage populations are critical for normal development and function of the mammary gland. Macrophages are versatile cells capable of diverse roles in mammary gland development and maintenance of homeostasis, and th...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-014-9319-7
更新日期:2014-07-01 00:00:00
abstract::Breast development occurs through well-defined stages representing 'windows of susceptibility' to adverse environmental exposures that potentially modify breast cancer risk. Systematic characterization of morphology and transcriptome during normal breast development lays the foundation of our understanding of cancer e...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章
doi:10.1007/s10911-018-9401-7
更新日期:2018-09-01 00:00:00