Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3
Rachel S. Chapman,Paula C. C. Lourenço,Elizabeth Tonner,David J. Flint,Stefan Selbert,Kiyoshi Takeda,Shizuo Akira,Alan Richard Clarke,Christine J. Watson +8 more
TL;DR: It is suggested that IGFBP-5 is a direct or indirect target for Stat3 and its upregulation is essential to normal involution, and the importance of a Stat factor in signaling the initiation of physiological apoptosis in vivo is demonstrated.
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Abstract: Mammary gland involution is characterized by extensive apoptosis of the epithelial cells At the onset of involution, Stat3 is specifically activated To address the function of this signaling molecule in mammary epithelial apoptosis, we have generated a conditional knockout of Stat3 using the Cre-lox recombination system Following weaning, a decrease in apoptosis and a dramatic delay of involution occurred in Stat3 null mammary tissue Involution is normally associated with a significant increase in IGFBP-5 levels This was observed in control glands, but not in the absence of Stat3 IGFBP-5 has been suggested to induce apoptosis by sequestering IGF-1 to casein micelles, thereby inhibiting its survival function Our findings suggest that IGFBP-5 is a direct or indirect target for Stat3 and its upregulation is essential to normal involution No marked differences were seen in the regulation of Stat5, Bcl-xL, or Bax in the absence of Stat3 Precocious activation of Stat1 and increases in levels of p53 and p21 occurred and may act as compensatory mechanisms for the eventual initiation of involution observed in Stat3 null mammary glands This is the first demonstration of the importance of a Stat factor in signaling the initiation of physiological apoptosis in vivo
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The role of STATs in transcriptional control and their impact on cellular function.
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Signaling through the JAK/STAT pathway, recent advances and future challenges.
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What does Stat3 do
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TL;DR: Recent data, especially from the analysis of conditional loss of Stat3 protein in adult tissues, confirm that Stat3 participates in a wide variety of physiological processes and even directs seemingly contradictory responses.
Mammary gland development
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TL;DR: The knowledge of mammary gland development and mammary stem cell biology has significantly contributed to the understanding of breast cancer and has advanced the discovery of therapies to treat this disease.
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References
Cell death : the significance of apoptosis
TL;DR: It has proved feasible to categorize most if not all dying cells into one or the other of two discrete and distinctive patterns of morphological change, which have, generally, been found to occur under disparate but individually characteristic circumstances.
7.7K
Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway
Marco A Meraz,Marco A Meraz,J. Michael White,Kathleen C. F. Sheehan,Erika A. Bach,Scott J. Rodig,Anand S. Dighe,Daniel H. Kaplan,Joan K. Riley,Andrew C. Greenlund,Dayle Campbell,Karen Carver-Moore,Raymond N. DuBois,Ross G. Clark,Michel Aguet,Michel Aguet,Robert D. Schreiber +16 more
TL;DR: These observations document that STAT1 plays an obligate and dedicated role in mediating IFN-dependent biologic responses and reveal an unexpected level of physiologic specificity for STAT1 action.
1.7K
STATs: signal transducers and activators of transcription.
TL;DR: Regarding biological functions, it can be anticipated that in the very near future the phenotypes of mice deficient in the remaining STATs will be described and will thus eliminate further speculation, and it would seem less likely as time goes on that additional family members will emerge.
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Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality
Kiyoshi Takeda,Koichi Noguchi,Wei Shi,Takashi Tanaka,Makoto Matsumoto,Nobuaki Yoshida,Tadamitsu Kishimoto,Shizuo Akira +7 more
TL;DR: It is demonstrated that Stat3 is essential for the early development of mouse embryos, and analysis of embryos at several gestation times revealed that stat3-deficient embryos showed a rapid degeneration between embryonic days 6.5 and 7.0.
1.4K
Stat5a and Stat5b Proteins Have Essential and Nonessential, or Redundant, Roles in Cytokine Responses
Stephan Teglund,Catriona McKay,Erin G. Schuetz,Jan M. van Deursen,Dimitrios J. Stravopodis,Demin Wang,Michael Brown,Sara Bodner,Gerard Grosveld,James N. Ihle,James N. Ihle +10 more
TL;DR: The phenotypes of the mice demonstrate an essential, and often redundant, role for the two Stat5 proteins in a spectrum of physiological responses associated with growth hormone and prolactin.
1.3K