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Breast Cancer Research : BCR 2009Myc has been intensely studied since its discovery more than 25 years ago. Insight has been gained into Myc's function in normal physiology, where its role appears to be... (Review)
Review
Myc has been intensely studied since its discovery more than 25 years ago. Insight has been gained into Myc's function in normal physiology, where its role appears to be organ specific, and in cancer where many mechanisms contribute to aberrant Myc expression. Numerous signals and pathways converge on Myc, which in turn acts on a continuously growing number of identified targets, via transcriptional and nontranscriptional mechanisms. This review will concentrate on Myc as a signaling mediator in the mammary gland, discussing its regulation and function during normal development, as well as its activation and roles in breast cancer.
Topics: Animals; Breast Neoplasms; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; Mammary Neoplasms, Experimental; Proto-Oncogene Proteins c-myc; Signal Transduction
PubMed: 19849814
DOI: 10.1186/bcr2406 -
Current Drug Targets Sep 2010The hedgehog signal transduction network is a critical regulator of metazoan development. Inappropriate activation of this network is implicated in several different... (Review)
Review
The hedgehog signal transduction network is a critical regulator of metazoan development. Inappropriate activation of this network is implicated in several different cancers, including breast. Genetic evidence in mice as well as molecular biological studies in human cells clearly indicate that activated signaling can lead to mammary hyperplasia and, in some cases, tumor formation. However, the exact role(s) activated hedgehog signaling plays in the development or progression of breast cancer also remain unclear. In this review, we have discussed recent data regarding the mechanism(s) by which the hedgehog network may signal in the mammary gland, as well as the data implicating activated signaling as a contributing factor to breast cancer development. Finally, we provide a brief update on the available hedgehog signaling inhibitors with respect to ongoing clinical trials, some of which will include locally advanced or metastatic breast cancers. Given the growing intensity with which the hedgehog signaling network is being studied in the normal and neoplastic mammary gland, a more complete understanding of this network should allow more effective targeting of its activities in breast cancer treatment or prevention.
Topics: Animals; Breast Neoplasms; Female; Hedgehog Proteins; Humans; Mammary Glands, Animal; Mammary Glands, Human; Mice; Mice, Knockout; Mice, Transgenic; Signal Transduction
PubMed: 20545610
DOI: 10.2174/138945010792006753 -
International Journal of Biological... 2014BRCA1 mainly acts as a tumor suppressor and BRCA1 mutation correlates with increased cancer risk. Although it is well recognized that BRCA1 related tumorigenesis is... (Review)
Review
BRCA1 mainly acts as a tumor suppressor and BRCA1 mutation correlates with increased cancer risk. Although it is well recognized that BRCA1 related tumorigenesis is mainly caused by the increased DNA damage and decreased genome stability, it is not clear that why BRCA1 related patients have higher risk for cancer development mainly in estrogen responsive tissues such as breast and ovary. Recent studies suggested that BRCA1 and E-ER (estrogen and estrogen receptor) signaling synergistically regulate the mammary epithelial cell proliferation and differentiation. In this current presentation, we reviewed the correlation between mammary gland epithelial cell transformation and the status of BRCA1 and ER. Then the mechanisms of BRCA1 and E-ER interaction at both gene transcription level and protein-protein interaction level are discussed. Furthermore, the tumorigenic mechanisms are discussed by focusing on the synergistic effect of BRCA1 and E-ER on cell metabolism, ROS management, and antioxidant activity in mammary gland epithelial cells. Also, the possibility of cell de-differentiation promoted by coordinated effect between BRCA1 mutation and E-ER signal is explored. Together, the currently available evidences suggest that BRCA1 mutation and E-ER signal together, contribute to breast tumorigenesis by providing the metabolic support for cancer cell growth and even may directly be involved in promoting the de-differentiation of cancer-prone epithelial cells.
Topics: Antioxidants; BRCA1 Protein; Breast Neoplasms; Carcinogenesis; Epithelial Cells; Estrogen Receptor alpha; Estrogens; Female; Humans; Mammary Glands, Human; Reactive Oxygen Species
PubMed: 24910535
DOI: 10.7150/ijbs.8579 -
The Breast Journal 2010The mammary gland, the unique organ that primarily form at puberty, is an ideal model to study the functions of homeobox (HB) genes in both development and...
The mammary gland, the unique organ that primarily form at puberty, is an ideal model to study the functions of homeobox (HB) genes in both development and tumorigenesis. HB genes comprise a large family of developmental regulators that have a critical role in cell growth and differentiation. In the normal mammary gland, homeobox genes are involved in ductal formation, epithelial branching, and lobulo-alveolar development by regulating epithelial proliferation and differentiation. The HB genes are controlled in a spatial and temporal manner in both stromal and epithelial cells. They are coordinately regulated by hormones and extracellular matrix, suggesting that many signaling pathways are involved in homeobox gene functions. When homeobox genes are misexpressed in animal models, different defects are displayed in mammary gland development. Aberrant expression of homeobox genes, overexpressed or downregulated, is found in primary carcinomas and in breast cancer. The Otx1 HB gene is a classic regulatory of nervous system development during embryogenesis. Postnatally Otx1 is transcribed in the anterior pituitary gland, where activates transcription of the pituitary hormones, and plays a role in hematopoiesis, enhancing pluripotent cells, and erythroid differentiation. Otx1 can still be detected in mature cells of the erythroid and megacaryocytic lineage. During cyclical development of mammary gland, the Otx1 gene is overexpressed in lactation, confirming a role of this transcription factor in cell differentiation. Recent studies report that Otx1 is overexpressed in breast cancer. Otx1 is expressed during embryogenesis, and it is expressed again during carcinogenesis, implying its possible function in differentiation of neoplastic cells.
Topics: Animals; Breast Neoplasms; Epithelial Cells; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; Neoplastic Stem Cells; Otx Transcription Factors
PubMed: 21050313
DOI: 10.1111/j.1524-4741.2010.01006.x -
Journal of Traditional Chinese Medicine... Dec 2022To explore the value and factors influencing the maintenance of valid Traditional Chinese Medicine compound prescription patents for the management of mammary gland...
OBJECTIVE
To explore the value and factors influencing the maintenance of valid Traditional Chinese Medicine compound prescription patents for the management of mammary gland hyperplasia.
METHODS
The State Intellectual Property Office Patents Database, China Patent Information Center Patents Database, Soopat Patent Search Platform, and CNIPR Search Platform of Chinese and Foreign Patent Database were searched to identify Traditional Chinese Medicine compound prescription patents for mammary gland hyperplasia that had been maintained for at least 5 years. Logistic regression analysis was used to detect the factors influencing the maintenance of valid patents.
RESULTS
From 1 January 1993 to 31 December 2019, a total of 1228, Traditional Chinese Medicine compound prescription patents for mammary gland hyperplasia were authorized. Of these applications, 381 patents were granted and only 176 patents were maintained for more than 5 years. The five independent variables assessed in this study all had significant explanatory functions.
CONCLUSIONS
The maintenance of valid patents for Traditional Chinese Medicine compound prescriptions for treating mammary gland hyperplasia is of great importance. The maintenance of such patents depends on many factors, such as the concentration of effective herbs, number of dependent claims, provision of new dosage forms and detailed experimental data, and transfer of patent rights.
Topics: Humans; Medicine, Chinese Traditional; Hyperplasia; Mammary Glands, Human; Drugs, Chinese Herbal; Prescriptions
PubMed: 36378061
DOI: 10.19852/j.cnki.jtcm.2022.06.010 -
Cell Death and Differentiation Feb 2017Mammary gland development, various stages of mammary tumorigenesis and breast cancer progression have the peptidyl-prolyl cis/trans isomerase PIN1 at their centerpiece,... (Review)
Review
Mammary gland development, various stages of mammary tumorigenesis and breast cancer progression have the peptidyl-prolyl cis/trans isomerase PIN1 at their centerpiece, in virtue of the ability of this unique enzyme to fine-tune the dynamic crosstalk between multiple molecular pathways. PIN1 exerts its action by inducing conformational and functional changes on key cellular proteins, following proline-directed phosphorylation. Through this post-phosphorylation signal transduction mechanism, PIN1 controls the extent and direction of the cellular response to a variety of inputs, in physiology and disease. This review discusses PIN1's roles in normal mammary development and cancerous progression, as well as the clinical impact of targeting this enzyme in breast cancer patients.
Topics: Breast Neoplasms; Drug Resistance, Neoplasm; E2F Transcription Factors; Enzyme Inhibitors; Female; Genomic Instability; Humans; Mammary Glands, Human; NIMA-Interacting Peptidylprolyl Isomerase; Signal Transduction
PubMed: 27834957
DOI: 10.1038/cdd.2016.122 -
Breast Cancer Research : BCR Jan 2017Macrophages play diverse roles in mammary gland development and breast cancer. CC-chemokine ligand 2 (CCL2) is an inflammatory cytokine that recruits macrophages to...
BACKGROUND
Macrophages play diverse roles in mammary gland development and breast cancer. CC-chemokine ligand 2 (CCL2) is an inflammatory cytokine that recruits macrophages to sites of injury. Although CCL2 has been detected in human and mouse mammary epithelium, its role in regulating mammary gland development and cancer risk has not been explored.
METHODS
Transgenic mice were generated wherein CCL2 is driven by the mammary epithelial cell-specific mouse mammary tumour virus 206 (MMTV) promoter. Estrous cycles were tracked in adult transgenic and non-transgenic FVB mice, and mammary glands collected at the four different stages of the cycle. Dissected mammary glands were assessed for cyclical morphological changes, proliferation and apoptosis of epithelium, macrophage abundance and collagen deposition, and mRNA encoding matrix remodelling enzymes. Another cohort of control and transgenic mice received carcinogen 7,12-Dimethylbenz(a)anthracene (DMBA) and tumour development was monitored weekly. CCL2 protein was also quantified in paired samples of human breast tissue with high and low mammographic density.
RESULTS
Overexpression of CCL2 in the mammary epithelium resulted in an increased number of macrophages, increased density of stroma and collagen and elevated mRNA encoding matrix remodelling enzymes lysyl oxidase (LOX) and tissue inhibitor of matrix metalloproteinases (TIMP)3 compared to non-transgenic controls. Transgenic mice also exhibited increased susceptibility to development of DMBA-induced mammary tumours. In a paired sample cohort of human breast tissue, abundance of epithelial-cell-associated CCL2 was higher in breast tissue of high mammographic density compared to tissue of low mammographic density.
CONCLUSIONS
Constitutive expression of CCL2 by the mouse mammary epithelium induces a state of low level chronic inflammation that increases stromal density and elevates cancer risk. We propose that CCL2-driven inflammation contributes to the increased risk of breast cancer observed in women with high mammographic density.
Topics: Animals; Breast Density; Breast Neoplasms; Chemokine CCL2; Chemotaxis, Leukocyte; Disease Models, Animal; Disease Susceptibility; Epithelium; Estrous Cycle; Female; Gene Expression; Humans; Inflammation; Kaplan-Meier Estimate; Macrophages; Mammary Glands, Human; Mammary Neoplasms, Experimental; Mice; Mice, Transgenic; Prognosis; RNA, Messenger; Stromal Cells
PubMed: 28077158
DOI: 10.1186/s13058-016-0796-z -
Journal of Mammary Gland Biology and... Jun 2008The ErbB receptor tyrosine kinase family has often been associated with increased growth of breast epithelial cells, as well as malignant transformation and progression.... (Review)
Review
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 kinase to a signal transduction mechanism that slows growth and stimulates differentiation of breast cells. This review provides an overview of ErbB4/HER4 in growth and differentiation of the mammary epithelium, including its physiologic role in development, the contrasting growth inhibition/tumor suppression and growth acceleration of distinct ErbB4/HER4 isoforms and a description of the unique cell cycle regulated pattern of nuclear HER4 ubiquitination and destruction.
Topics: Animals; Biomarkers, Tumor; Breast Neoplasms; Cell Differentiation; ErbB Receptors; Female; Growth Inhibitors; Humans; Mammary Glands, Animal; Mammary Glands, Human; Mice; Protein Isoforms; Receptor, ErbB-4; Signal Transduction; Tumor Cells, Cultured
PubMed: 18437540
DOI: 10.1007/s10911-008-9080-x -
Cold Spring Harbor Perspectives in... Mar 2011Leukocytes, of both the innate and adaptive lineages, are normal cellular components of all tissues. These important cells not only are critical for regulating normal... (Review)
Review
Leukocytes, of both the innate and adaptive lineages, are normal cellular components of all tissues. These important cells not only are critical for regulating normal tissue homeostasis, but also are significant paracrine regulators of all physiologic and pathologic tissue repair processes. This article summarizes recent insights regarding the trophic roles of leukocytes at each stage of mammary gland development and during cancer development, with a focus on Murids and humans.
Topics: Animals; Breast Neoplasms; Collagen; Eosinophils; Female; Humans; Immunity, Humoral; Lactation; Leukocytes; Macrophages; Mammary Glands, Human; Mast Cells; Mice; Myeloid Cells; Pregnancy; T-Lymphocytes
PubMed: 21123394
DOI: 10.1101/cshperspect.a003285 -
Cold Spring Harbor Perspectives in... Aug 2012Remarkable strides have been made in understanding the role of the extracellular matrix in mammary gland biology. But future efforts should employ a more physiologically... (Review)
Review
Remarkable strides have been made in understanding the role of the extracellular matrix in mammary gland biology. But future efforts should employ a more physiologically relevant model system (i.e., a non-culture-based system).
Topics: Breast Neoplasms; Cell Adhesion; Cellular Microenvironment; Extracellular Matrix; Female; Humans; Integrins; Intercellular Junctions; Intercellular Signaling Peptides and Proteins; Mammary Glands, Human; Signal Transduction
PubMed: 22855728
DOI: 10.1101/cshperspect.a013540