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פותח על ידי קלירמאש פתרונות בע"מ -
Forced activation of Stat5 subjects mammary epithelial cells to DNA damage and preferential induction of the cellular response mechanism during proliferation
Year:
2011
Source of publication :
Journal of Cellular Physiology
Authors :
אילון, טלי
;
.
ברש, איתמר
;
.
Volume :
226
Co-Authors:
Eilon, T., Institute of Animal Science, ARO, Volcani Center, Bet-Dagan, Israel
Barash, I., Institute of Animal Science, ARO, Volcani Center, Bet-Dagan, Israel
Facilitators :
From page:
616
To page:
626
(
Total pages:
11
)
Abstract:
Parity-dependent adenocarcinoma tumors developed in postestropausal transgenic mice expressing a constitutively active Stat5 variant (STAT5ca) in their mammary gland. These tumors maintained elevated expression levels of genes regulating the cellular DNA damage response (DDR) mechanism, compared to the intact gland. No correlation with STAT5ca expression was observed for these genes in the established tumors. However, activated Stat5a in individual cells of the rarely and earlier developed hyperplasia was associated with induced Chk2 activity. Deregulated Stat5 may already cause DNA damage during the fertile period. This hypothesis and the specific vulnerable stage were further studied in mammary epithelial cells that were stably transfected with β-lactoglobulin (BLG)/STAT5ca and exposed to a reproduced reproductive cycle. During the pregnancy-like proliferative state, STAT5ca expression was induced by the added lactogenic hormones. Production of reactive oxygen species, rather than proliferation, served as the primary mediator of DNA damage and cellular DDR. Differentiated cells expressed higher levels of STAT5ca and retained the DNA nicks. However, the elevated expression of the genes involved in DDR was downregulated. Higher levels of DNA damage were also detected in the mammary gland of transgenic mice expressing the BLG/STAT5ca during pregnancy and lactation. However, the relative number of damaged cells was much lower than that in the reproduced in vitro stages and the insults were generally associated with apoptosis and DDR. This study implicates pregnancy as the vulnerable stage for deregulated Stat5 activity, and demonstrates that DNA insults in viable differentiated mammary epithelial cells are ignored by the DDR mechanism. © 2010 Wiley-Liss, Inc.
Note:
Related Files :
animal cell
Animals
animal tissue
Cell Proliferation
checkpoint kinase 2
Female
Mammary Neoplasms, Animal
mice
unclassified drug
עוד תגיות
תוכן קשור
More details
DOI :
10.1002/jcp.22381
Article number:
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
21017
Last updated date:
02/03/2022 17:27
Creation date:
16/04/2018 23:40
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Scientific Publication
Forced activation of Stat5 subjects mammary epithelial cells to DNA damage and preferential induction of the cellular response mechanism during proliferation
226
Eilon, T., Institute of Animal Science, ARO, Volcani Center, Bet-Dagan, Israel
Barash, I., Institute of Animal Science, ARO, Volcani Center, Bet-Dagan, Israel
Forced activation of Stat5 subjects mammary epithelial cells to DNA damage and preferential induction of the cellular response mechanism during proliferation
Parity-dependent adenocarcinoma tumors developed in postestropausal transgenic mice expressing a constitutively active Stat5 variant (STAT5ca) in their mammary gland. These tumors maintained elevated expression levels of genes regulating the cellular DNA damage response (DDR) mechanism, compared to the intact gland. No correlation with STAT5ca expression was observed for these genes in the established tumors. However, activated Stat5a in individual cells of the rarely and earlier developed hyperplasia was associated with induced Chk2 activity. Deregulated Stat5 may already cause DNA damage during the fertile period. This hypothesis and the specific vulnerable stage were further studied in mammary epithelial cells that were stably transfected with β-lactoglobulin (BLG)/STAT5ca and exposed to a reproduced reproductive cycle. During the pregnancy-like proliferative state, STAT5ca expression was induced by the added lactogenic hormones. Production of reactive oxygen species, rather than proliferation, served as the primary mediator of DNA damage and cellular DDR. Differentiated cells expressed higher levels of STAT5ca and retained the DNA nicks. However, the elevated expression of the genes involved in DDR was downregulated. Higher levels of DNA damage were also detected in the mammary gland of transgenic mice expressing the BLG/STAT5ca during pregnancy and lactation. However, the relative number of damaged cells was much lower than that in the reproduced in vitro stages and the insults were generally associated with apoptosis and DDR. This study implicates pregnancy as the vulnerable stage for deregulated Stat5 activity, and demonstrates that DNA insults in viable differentiated mammary epithelial cells are ignored by the DDR mechanism. © 2010 Wiley-Liss, Inc.
Scientific Publication
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