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 etiology. We examined mammary glands in female Sprague Dawley rats across six developmental stages - pre-pubertal, peri-pubertal, pubertal, lactation, adult parous and adult nulliparous. We investigated histology by Hematoxylin and Eosin and Mallory's Trichrome stain, proliferative and apoptotic rate by immunohistochemistry and whole-transcriptome by microarrays. We identified differentially expressed genes between adjacent developmental stages by linear models, underlying pathways by gene ontology analysis and gene networks and hubs active across developmental stages by coexpression network analysis. Mammary gland development was associated with large-scale changes in the transcriptome; particularly from pre-pubertal to peri-pubertal period and the lactation period were characterized by distinct patterns of gene expression with unique biological functions such as immune processes during pre-pubertal development and cholesterol biosynthesis during lactation. These changes were reflective of the shift in mammary gland histology, from a rudimentary organ during early stages to a secretory organ during lactation followed by regression with age. Hub genes within mammary gene networks included metabolic genes such as Pparg during the pre-pubertal stage and tight junction-related genes claudins and occludins in lactating mammary glands. Transcriptome profile paired with histology enhanced our understanding of mammary development, which is fundamental in understanding the etiologic mechanism of breast cancer, especially pertaining to windows of susceptibility to environmental exposures that may alter breast cancer risk.
journal_name
J Mammary Gland Biol Neoplasiajournal_title
Journal of mammary gland biology and neoplasiaauthors
Gopalakrishnan K,Teitelbaum SL,Wetmur J,Manservisi F,Falcioni L,Panzacchi S,Gnudi F,Belpoggi F,Chen Jdoi
10.1007/s10911-018-9401-7subject
Has Abstractpub_date
2018-09-01 00:00:00pages
149-163issue
3eissn
1083-3021issn
1573-7039pii
10.1007/s10911-018-9401-7journal_volume
23pub_type
杂志文章abstract::Postpartum mammary gland involution is a mammalian tissue remodeling event that occurs after pregnancy and lactation to return the gland to the pre-pregnant state. This event is characterized by apoptosis and lysosomal-mediated cell death of the majority of the lactational mammary epithelium, followed by remodeling of...
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journal_title:Journal of mammary gland biology and neoplasia
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journal_title:Journal of mammary gland biology and neoplasia
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doi:10.1023/a:1009546811429
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journal_title:Journal of mammary gland biology and neoplasia
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doi:10.1007/s10911-015-9348-x
更新日期:2016-06-01 00:00:00
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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
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journal_title:Journal of mammary gland biology and neoplasia
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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::Obesity is a preventable risk factor for breast cancer following menopause. Regardless of menopausal status, obese women who develop breast cancer have a worsened prognosis. Breast tissue is comprised of mammary epithelial cells organized into ducts and lobules and surrounded by adipose-rich connective tissue. Studies...
journal_title:Journal of mammary gland biology and neoplasia
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doi:10.1007/s10911-020-09452-5
更新日期:2020-06-01 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
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doi:10.1007/s10911-007-9043-7
更新日期:2007-09-01 00:00:00
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journal_title:Journal of mammary gland biology and neoplasia
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doi:10.1023/a:1020308104613
更新日期:2002-04-01 00:00:00
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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
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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::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::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
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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
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journal_title:Journal of mammary gland biology and neoplasia
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journal_title:Journal of mammary gland biology and neoplasia
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更新日期:2018-06-01 00:00:00
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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
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journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-021-09478-3
更新日期:2021-01-21 00:00:00
abstract::The insulin-like growth factors (IGFs) signaling via the type I insulin-like growth factor receptor (IGF-1R) regulate multiple aspects of malignancy. The importance of IGF-1R in regulating the malignant phenotype is currently being validated in numerous clinical trials for cancer including breast cancer. This review d...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-008-9105-5
更新日期:2008-12-01 00:00:00
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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::Exosomes are small extracellular vesicles secreted to the extracellular environment by several cell types, including tumor cells. It has been demonstrated that exosomes have an important role in intercellular communication, but they have recently been implicated in various tumor processes, including the oncogenic tran...
journal_title:Journal of mammary gland biology and neoplasia
pub_type: 杂志文章,评审
doi:10.1007/s10911-015-9332-5
更新日期:2014-12-01 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
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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 mouse model for breast cancer has developed into a most effective means of dissecting and understanding this devastating disease. The inbred transgenic mouse lends itself to biological, molecular, immunological, and genetic studies. The observation, dissection, transplantation, and subsequent amplification of prec...
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pub_type: 杂志文章,评审
doi:10.1007/s10911-008-9088-2
更新日期:2008-09-01 00:00:00