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 govern this event remains inadequate. Clinically, ~30% of breast cancer patients diagnosed with early-stage disease undergo metastatic progression, an event that (a) severely limits treatment options, (b) typically results in chemoresistance and low response rates, and (c) greatly contributes to aggressive relapses and dismal survival rates. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that regulates all phases of postnatal mammary gland development, including branching morphogenesis, lactation, and involution. TGF-β also plays a prominent role in suppressing mammary tumorigenesis by preventing mammary epithelial cell (MEC) proliferation, or by inducing MEC apoptosis. Genetic and epigenetic events that transpire during mammary tumorigenesis conspire to circumvent the tumor suppressing activities of TGF-β, thereby permitting late-stage breast cancer cells to acquire invasive and metastatic phenotypes in response to TGF-β. Metastatic progression stimulated by TGF-β also relies on its ability to induce epithelial-mesenchymal transition (EMT) and the expansion of chemoresistant breast cancer stem cells. Precisely how this metamorphosis in TGF-β function comes about remains incompletely understood; however, recent findings indicate that the initiation of oncogenic TGF-β activity is contingent upon imbalances between its canonical and noncanonical signaling systems. Here we review the molecular and cellular contributions of noncanonical TGF-β effectors to mammary tumorigenesis and metastatic progression.
journal_name
J Mammary Gland Biol Neoplasiajournal_title
Journal of mammary gland biology and neoplasiaauthors
Parvani JG,Taylor MA,Schiemann WPdoi
10.1007/s10911-011-9207-3subject
Has Abstractpub_date
2011-06-01 00:00:00pages
127-46issue
2eissn
1083-3021issn
1573-7039journal_volume
16pub_type
杂志文章,评审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::Milk production is highly dependent on the optimal development of the mammary epithelium. It is therefore essential to better understand mammary epithelial cell growth and maintenance from the related epithelial lineage during the animal life. Here, we characterized the epithelial lineage at puberty, lactation and dry...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章
doi:10.1007/s10911-019-09427-1
更新日期:2019-06-01 00:00:00
abstract::Tumor spread involves degradation of various components of the extracellular matrix and blood vessel wall. Among these is heparan sulfate proteoglycan, which plays a key role in the self-assembly, insolubility and barrier properties of basement membranes and extracellular matrices. Expression of an endoglycosidase (he...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1011375624902
更新日期:2001-07-01 00:00:00
abstract::Mammary gland involution, characterized by extensive apoptosis and structural remodelling of the gland, is the process by which the gland is returned to the pre-pregnant state. A key advantage of the mammary gland is the ability to synchronize involution through forced weaning, thus allowing the dissection of biochemi...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-007-9034-8
更新日期:2007-03-01 00:00:00
abstract::The potential role of smoking in breast cancer risk has been the subject of over 100 publications, numerous scientific reviews, and animated debate. Tobacco exposure is a well-established cause of lung cancer, and is thought to account for nearly one third of all cancer deaths. Tobacco smoke contains thousands of chem...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-012-9269-x
更新日期:2013-03-01 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
abstract::Transforming growth factor beta (TGF-beta) receptor expression and signal transduction in human breast cancer are reviewed as a function of estrogen receptor (ER) expression. ER+ breast cancer cells are generally resistant to the inhibitory effects of TGF-beta. The only known exception appears to be MCF-7 early passag...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/BF02017392
更新日期:1996-10-01 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::Breast cancer development is a multi-step process in which genetic and molecular heterogeneity occurs at multiple stages. Ductal carcinoma arises from pre-invasive lesions such as atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), which progress to invasive and metastatic cancer. The feasibility of...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-018-9408-0
更新日期:2018-12-01 00:00:00
abstract::Women are using estrogens for many purposes, such as to prevent pregnancy or miscarriage, or to treat menopausal symptoms. Estrogens also have been used to treat breast cancer which seems puzzling, since there is convincing evidence to support a link between high lifetime estrogen exposure and increased breast cancer ...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-013-9274-8
更新日期:2013-03-01 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::Mouse modeling of human breast cancer has developed tremendously over the past ten years. Human breast cancer is characterized by enormous biological diversity and, collectively, the new models have come much closer to encompassing this diversity. They have provided a deeper understanding of the fundamental events tha...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-008-9093-5
更新日期:2008-09-01 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::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::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::Breast cancer is one of the most common cancers of women in the Western world. Despite modest achievements in the treatment of this disease, there is a substantial unmet medical need to reduce the occurrence of new breast cancers. In several prospective, placebo-controlled trials, the antiestrogen tamoxifen has been s...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1025727103811
更新日期:2003-01-01 00:00:00
abstract::The relationship between maternal dietary intakes of energy or fat maternal body composition and the milk fat concentration is an important element in understanding the role of breast-milk in infant nutrition. In most studies in both developing and developed countries, no relation between maternal energy intake and mi...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章
doi:10.1023/a:1018702030259
更新日期:1999-07-01 00:00:00
abstract::Wild-type p53 is a tumor suppressor gene that plays a central role in maintaining the genetic integrity of the cell by preventing cells with damaged DNA from further proliferation. Mutation and deletion of p53 are the most common genetic defects seen in clinical cancer. About 40% of breast carcinomas show high levels ...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/BF02013640
更新日期:1996-04-01 00:00:00
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 tr...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章
doi:10.1007/s10911-018-9407-1
更新日期:2018-12-01 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::Normal mammary gland development is the result of complex interactions between a number of hormones and growth factors. Normal and malignant human mammary epithelial cells are able to synthesize and to respond to various different, locally acting growth factors and growth inhibitors. Among these, the EGF-related pepti...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1026351730785
更新日期:1997-04-01 00:00:00
abstract::As their name implies, the myoepithelial cells found at the epithelial-mesenchymal interface of the human mammary gland disclose features suggestive of a dual epithelial-like and muscle-like differentiation, i.e. they co-express various keratins and vimentin intermediate filaments, as well as smooth muscle-related ant...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-005-9581-9
更新日期:2005-07-01 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::Calcium is an important nutrient that is secreted into milk in quantities that put a considerable stress upon maternal calcium homeostasis. Here we summarize the evidence that two important entities, the extracellular calcium-sensing receptor (CaR) and parathyroid hormone-related protein (PTHrP) are involved in a feed...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-005-5396-y
更新日期:2005-04-01 00:00:00
abstract::Since breast cancer and its associated metastasis are a global health problem and a major cause of mortality among women, research efforts to understand the development, morphogenesis, and functioning of the mammary gland are a high priority. Myriad signaling pathways, transcription factors, and associated transcripti...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-007-9043-7
更新日期:2007-09-01 00:00:00
abstract::With our improved understanding of the biological behavior of breast cancer, minimally invasive intervention is urgently needed for personalized treatment of early disease. Intraductal therapy is one such minimally invasive approach. With the help of appropriate tools, technologies using the intraductal means of enter...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-020-09453-4
更新日期:2020-06-01 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::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::The IGFBP family comprises six proteins with high affinity for the IGFs and several lower affinity IGFBP-related proteins. Their production in the breast is controlled by hormones, other local regulators and in tumors relates to the estrogen receptor status. Their functional activity can also be affected by various po...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1023/a:1009519400591
更新日期:2000-01-01 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