Role of DDC-4/sFRP-4, a secreted Frizzled-related protein, at the onset of apoptosis in mammary involution
Using differential display, we isolated DDC-4, a s ecreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus. The role of this gene in apoptosis was studied in anima...
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| Veröffentlicht in: | Cell death and differentiation 2003-05, Vol.10 (5), p.528-538 |
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| container_title | Cell death and differentiation |
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| creator | Lacher, M D Siegenthaler, A Jäger, R Yan, Xi Hett, S Xuan, L Saurer, S Lareu, R R Dharmarajan, A M Friis, R |
| description | Using differential display, we isolated DDC-4, a
s
ecreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus. The role of this gene in apoptosis was studied in animals overexpressing ectopic DDC-4/sFRP-4. Transgenic mice bearing the
DDC-4/sFRP-4
cDNA under the control of the MMTV-LTR promoter showed lactational insufficiency and many apoptotic cells in the alveoli between day 19 of pregnancy and day 4 of lactation as demonstrated by TUNEL reaction and the presence of activated caspase-3. We performed a PKB/Akt kinase assay and studied several of its substrates using phosphorylation-specific antibodies to show reduced phosphorylation in PKB/Akt itself, as well as in glycogen synthetase kinase-3
β
(GSK-3
β
), BAD, and Forkhead. Taken together, our results show a role for DDC-4/sFRP-4 in abrogating an epithelial cell survival pathway at the onset of mammary gland involution. |
| doi_str_mv | 10.1038/sj.cdd.4401197 |
| format | Article |
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s
ecreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus. The role of this gene in apoptosis was studied in animals overexpressing ectopic DDC-4/sFRP-4. Transgenic mice bearing the
DDC-4/sFRP-4
cDNA under the control of the MMTV-LTR promoter showed lactational insufficiency and many apoptotic cells in the alveoli between day 19 of pregnancy and day 4 of lactation as demonstrated by TUNEL reaction and the presence of activated caspase-3. We performed a PKB/Akt kinase assay and studied several of its substrates using phosphorylation-specific antibodies to show reduced phosphorylation in PKB/Akt itself, as well as in glycogen synthetase kinase-3
β
(GSK-3
β
), BAD, and Forkhead. Taken together, our results show a role for DDC-4/sFRP-4 in abrogating an epithelial cell survival pathway at the onset of mammary gland involution.</description><identifier>ISSN: 1350-9047</identifier><identifier>EISSN: 1476-5403</identifier><identifier>DOI: 10.1038/sj.cdd.4401197</identifier><identifier>PMID: 12728251</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Apoptosis ; Apoptosis - physiology ; bcl-Associated Death Protein ; Biochemistry ; Biomedical and Life Sciences ; Breastfeeding & lactation ; Carrier Proteins - metabolism ; Caspase 3 ; Caspases - metabolism ; Cell Biology ; Cell Cycle Analysis ; Cell death ; Cell Line ; Cell Survival - physiology ; Cells, Cultured ; Electrophoresis, Polyacrylamide Gel ; Epithelial Cells - cytology ; Epithelial Cells - metabolism ; Female ; Fibroblasts ; Forkhead Transcription Factors ; Genes ; Glycogen Synthase Kinase 3 - metabolism ; Glycogen Synthase Kinase 3 beta ; Kinases ; Life Sciences ; Ligands ; Mammary Glands, Animal - cytology ; Mammary Glands, Animal - physiology ; Membrane Proteins - genetics ; Membrane Proteins - physiology ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Nuclear Proteins - metabolism ; original-paper ; Phenotype ; Phosphorylation ; Physiology ; Prostate ; Protein-Serine-Threonine Kinases ; Proteins ; Proteins - physiology ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-akt ; Signal transduction ; Stem Cells ; Transcription Factors - metabolism ; Transgenes - genetics ; Transgenic animals</subject><ispartof>Cell death and differentiation, 2003-05, Vol.10 (5), p.528-538</ispartof><rights>Springer Nature Limited 2003</rights><rights>Copyright Nature Publishing Group May 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-73516a65fd3c08581d9fac894ef93c8a773aaff03c64b481d49026e366e1fbfa3</citedby><cites>FETCH-LOGICAL-c464t-73516a65fd3c08581d9fac894ef93c8a773aaff03c64b481d49026e366e1fbfa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.cdd.4401197$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.cdd.4401197$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12728251$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lacher, M D</creatorcontrib><creatorcontrib>Siegenthaler, A</creatorcontrib><creatorcontrib>Jäger, R</creatorcontrib><creatorcontrib>Yan, Xi</creatorcontrib><creatorcontrib>Hett, S</creatorcontrib><creatorcontrib>Xuan, L</creatorcontrib><creatorcontrib>Saurer, S</creatorcontrib><creatorcontrib>Lareu, R R</creatorcontrib><creatorcontrib>Dharmarajan, A M</creatorcontrib><creatorcontrib>Friis, R</creatorcontrib><title>Role of DDC-4/sFRP-4, a secreted Frizzled-related protein, at the onset of apoptosis in mammary involution</title><title>Cell death and differentiation</title><addtitle>Cell Death Differ</addtitle><addtitle>Cell Death Differ</addtitle><description>Using differential display, we isolated DDC-4, a
s
ecreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus. The role of this gene in apoptosis was studied in animals overexpressing ectopic DDC-4/sFRP-4. Transgenic mice bearing the
DDC-4/sFRP-4
cDNA under the control of the MMTV-LTR promoter showed lactational insufficiency and many apoptotic cells in the alveoli between day 19 of pregnancy and day 4 of lactation as demonstrated by TUNEL reaction and the presence of activated caspase-3. We performed a PKB/Akt kinase assay and studied several of its substrates using phosphorylation-specific antibodies to show reduced phosphorylation in PKB/Akt itself, as well as in glycogen synthetase kinase-3
β
(GSK-3
β
), BAD, and Forkhead. Taken together, our results show a role for DDC-4/sFRP-4 in abrogating an epithelial cell survival pathway at the onset of mammary gland involution.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>bcl-Associated Death Protein</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Breastfeeding & lactation</subject><subject>Carrier Proteins - metabolism</subject><subject>Caspase 3</subject><subject>Caspases - metabolism</subject><subject>Cell Biology</subject><subject>Cell Cycle Analysis</subject><subject>Cell death</subject><subject>Cell Line</subject><subject>Cell Survival - physiology</subject><subject>Cells, Cultured</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - metabolism</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Forkhead Transcription Factors</subject><subject>Genes</subject><subject>Glycogen Synthase Kinase 3 - metabolism</subject><subject>Glycogen Synthase Kinase 3 beta</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>Ligands</subject><subject>Mammary Glands, Animal - cytology</subject><subject>Mammary Glands, Animal - physiology</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - physiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Transgenic</subject><subject>Nuclear Proteins - metabolism</subject><subject>original-paper</subject><subject>Phenotype</subject><subject>Phosphorylation</subject><subject>Physiology</subject><subject>Prostate</subject><subject>Protein-Serine-Threonine Kinases</subject><subject>Proteins</subject><subject>Proteins - physiology</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-akt</subject><subject>Signal transduction</subject><subject>Stem Cells</subject><subject>Transcription Factors - metabolism</subject><subject>Transgenes - 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physiology</topic><topic>bcl-Associated Death Protein</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Breastfeeding & lactation</topic><topic>Carrier Proteins - metabolism</topic><topic>Caspase 3</topic><topic>Caspases - metabolism</topic><topic>Cell Biology</topic><topic>Cell Cycle Analysis</topic><topic>Cell death</topic><topic>Cell Line</topic><topic>Cell Survival - physiology</topic><topic>Cells, Cultured</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - metabolism</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Forkhead Transcription Factors</topic><topic>Genes</topic><topic>Glycogen Synthase Kinase 3 - metabolism</topic><topic>Glycogen Synthase Kinase 3 beta</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Ligands</topic><topic>Mammary Glands, Animal - cytology</topic><topic>Mammary Glands, Animal - physiology</topic><topic>Membrane Proteins - 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Academic</collection><jtitle>Cell death and differentiation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lacher, M D</au><au>Siegenthaler, A</au><au>Jäger, R</au><au>Yan, Xi</au><au>Hett, S</au><au>Xuan, L</au><au>Saurer, S</au><au>Lareu, R R</au><au>Dharmarajan, A M</au><au>Friis, R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of DDC-4/sFRP-4, a secreted Frizzled-related protein, at the onset of apoptosis in mammary involution</atitle><jtitle>Cell death and differentiation</jtitle><stitle>Cell Death Differ</stitle><addtitle>Cell Death Differ</addtitle><date>2003-05-01</date><risdate>2003</risdate><volume>10</volume><issue>5</issue><spage>528</spage><epage>538</epage><pages>528-538</pages><issn>1350-9047</issn><eissn>1476-5403</eissn><abstract>Using differential display, we isolated DDC-4, a
s
ecreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus. The role of this gene in apoptosis was studied in animals overexpressing ectopic DDC-4/sFRP-4. Transgenic mice bearing the
DDC-4/sFRP-4
cDNA under the control of the MMTV-LTR promoter showed lactational insufficiency and many apoptotic cells in the alveoli between day 19 of pregnancy and day 4 of lactation as demonstrated by TUNEL reaction and the presence of activated caspase-3. We performed a PKB/Akt kinase assay and studied several of its substrates using phosphorylation-specific antibodies to show reduced phosphorylation in PKB/Akt itself, as well as in glycogen synthetase kinase-3
β
(GSK-3
β
), BAD, and Forkhead. Taken together, our results show a role for DDC-4/sFRP-4 in abrogating an epithelial cell survival pathway at the onset of mammary gland involution.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>12728251</pmid><doi>10.1038/sj.cdd.4401197</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cell death and differentiation, 2003-05, Vol.10 (5), p.528-538 |
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| subjects | Animals Apoptosis Apoptosis - physiology bcl-Associated Death Protein Biochemistry Biomedical and Life Sciences Breastfeeding & lactation Carrier Proteins - metabolism Caspase 3 Caspases - metabolism Cell Biology Cell Cycle Analysis Cell death Cell Line Cell Survival - physiology Cells, Cultured Electrophoresis, Polyacrylamide Gel Epithelial Cells - cytology Epithelial Cells - metabolism Female Fibroblasts Forkhead Transcription Factors Genes Glycogen Synthase Kinase 3 - metabolism Glycogen Synthase Kinase 3 beta Kinases Life Sciences Ligands Mammary Glands, Animal - cytology Mammary Glands, Animal - physiology Membrane Proteins - genetics Membrane Proteins - physiology Mice Mice, Inbred BALB C Mice, Transgenic Nuclear Proteins - metabolism original-paper Phenotype Phosphorylation Physiology Prostate Protein-Serine-Threonine Kinases Proteins Proteins - physiology Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-akt Signal transduction Stem Cells Transcription Factors - metabolism Transgenes - genetics Transgenic animals |
| title | Role of DDC-4/sFRP-4, a secreted Frizzled-related protein, at the onset of apoptosis in mammary involution |
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