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Expression of a carboxy terminally truncated Stat5 with no transactivation domain in the mammary glands of transgenic mice inhibits cell proliferation during pregnancy, delays onset of milk secretion, and induces apoptosis upon involution
Year:
2006
Authors :
Barash, Itamar
;
.
Eilon, Tali
;
.
Volume :
73
Co-Authors:
Iavnilovitch, E., Institute of Animal Science, ARO, Volcani Center, Bet Dagan, Israel
Eilon, T., Institute of Animal Science, ARO, Volcani Center, Bet Dagan, Israel
Groner, B., Georg Speyer Haus, Institute for Biomedical Research, Frankfurt/M, Germany
Barash, I., Institute of Animal Science, ARO, Volcani Center, Bet Dagan, Israel, Institute of Animal Science, ARO, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Facilitators :
From page:
841
To page:
849
(
Total pages:
9
)
Abstract:
Signal transducer and activator of transcription (Stat5) is a transcription factor, which transduces extracellular cytokine and growth-factor signals to the nuclei of mammalian cells. As a major mediator of prolactin action, it is involved in the regulation of the development, function, and survival of mammary epithelial cells. The carboxyl terminal of Stat5 encodes a transactivation domain (TAD), which interacts with coactivators and is crucial for the transcriptional induction of Stat5 target genes. To study the role of the Stat5 TAD in mediating Stat5 functions, a carboxy terminally truncated Stat5 variant (Stat5Δ750) was directed for expression in the mammary glands of transgenic mice by regulatory sequences of the β-lactoglobulin (BLG) gene. Expression of Stat5Δ750 in mammary tissue reduced the rates of cell proliferation at mid and late pregnancy. Subsequently, morphological signs of milk secretion upon parturition were delayed. In double-transgenic mice, expression of Stat5Δ750 drastically decreased BLG/luciferase activity during lactation, but did not affect the expression and secretion of the endogenous β-casein or α-lactalbumin into the milk. Expression of Stat5Δ750 also caused an increase in the number of apoptotic cells during mammary involution by a factor of 3 relative to control glands. Our data established a role for the Stat5 TAD in mediating the effects of Stat5 on mammary development, regulation of milk protein gene activity, and cell survival. The full effects of Stat5Δ750 may be partially buffered by the expression of endogenous wild-type Stat5 and the formation of truncated and wild-type heterodimers. © 2006 Wiley-Liss, Inc.
Note:
Related Files :
Animals
apoptosis
Female
lactation
Male
mice
milk
phenotype
pregnancy
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More details
DOI :
10.1002/mrd.20479
Article number:
Affiliations:
Database:
Scopus
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
23105
Last updated date:
02/03/2022 17:27
Creation date:
16/04/2018 23:56
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Scientific Publication
Expression of a carboxy terminally truncated Stat5 with no transactivation domain in the mammary glands of transgenic mice inhibits cell proliferation during pregnancy, delays onset of milk secretion, and induces apoptosis upon involution
73
Iavnilovitch, E., Institute of Animal Science, ARO, Volcani Center, Bet Dagan, Israel
Eilon, T., Institute of Animal Science, ARO, Volcani Center, Bet Dagan, Israel
Groner, B., Georg Speyer Haus, Institute for Biomedical Research, Frankfurt/M, Germany
Barash, I., Institute of Animal Science, ARO, Volcani Center, Bet Dagan, Israel, Institute of Animal Science, ARO, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Expression of a carboxy terminally truncated Stat5 with no transactivation domain in the mammary glands of transgenic mice inhibits cell proliferation during pregnancy, delays onset of milk secretion, and induces apoptosis upon involution
Signal transducer and activator of transcription (Stat5) is a transcription factor, which transduces extracellular cytokine and growth-factor signals to the nuclei of mammalian cells. As a major mediator of prolactin action, it is involved in the regulation of the development, function, and survival of mammary epithelial cells. The carboxyl terminal of Stat5 encodes a transactivation domain (TAD), which interacts with coactivators and is crucial for the transcriptional induction of Stat5 target genes. To study the role of the Stat5 TAD in mediating Stat5 functions, a carboxy terminally truncated Stat5 variant (Stat5Δ750) was directed for expression in the mammary glands of transgenic mice by regulatory sequences of the β-lactoglobulin (BLG) gene. Expression of Stat5Δ750 in mammary tissue reduced the rates of cell proliferation at mid and late pregnancy. Subsequently, morphological signs of milk secretion upon parturition were delayed. In double-transgenic mice, expression of Stat5Δ750 drastically decreased BLG/luciferase activity during lactation, but did not affect the expression and secretion of the endogenous β-casein or α-lactalbumin into the milk. Expression of Stat5Δ750 also caused an increase in the number of apoptotic cells during mammary involution by a factor of 3 relative to control glands. Our data established a role for the Stat5 TAD in mediating the effects of Stat5 on mammary development, regulation of milk protein gene activity, and cell survival. The full effects of Stat5Δ750 may be partially buffered by the expression of endogenous wild-type Stat5 and the formation of truncated and wild-type heterodimers. © 2006 Wiley-Liss, Inc.
Scientific Publication
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