Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

 
 
DownloadE-Mail
  Impaired CK1 Delta Activity Attenuates SV40-Induced Cellular Transformation In Vitro and Mouse Mammary Carcinogenesis In Vivo

Hirner, H., Guenes, C., Bischof, J., Wolff, S., Grothey, A., Kueh, M., et al. (2012). Impaired CK1 Delta Activity Attenuates SV40-Induced Cellular Transformation In Vitro and Mouse Mammary Carcinogenesis In Vivo. PLOS ONE, 7(1): e29709, pp. [1]-[16]. doi:10.1371/journal.pone.0029709.

Item is

Dateien

einblenden: Dateien
ausblenden: Dateien
:
journal.pone.0029709.pdf (beliebiger Volltext), 2MB
Name:
journal.pone.0029709.pdf
Beschreibung:
-
OA-Status:
Sichtbarkeit:
Öffentlich
MIME-Typ / Prüfsumme:
application/pdf / [MD5]
Technische Metadaten:
Copyright Datum:
-
Copyright Info:
open access article
Lizenz:
-

Externe Referenzen

einblenden:

Urheber

einblenden:
ausblenden:
 Urheber:
Hirner, Heidrun1, Autor
Guenes, Cagatay1, Autor
Bischof, Joachim1, Autor
Wolff, Sonja1, Autor
Grothey, Arnhild1, Autor
Kueh, Marion1, Autor
Oswald, Franz1, Autor
Wegwitz, Florian1, Autor
Boesl, Michael R.2, Autor           
Trauzold, Anna1, Autor
Henne-Bruns, Doris1, Autor
Peifer, Christian1, Autor
Leithaeuser, Frank1, Autor
Deppert, Wolfgang1, Autor
Knippschild, Uwe1, Autor
Affiliations:
1External Organizations, ou_persistent22              
2Department: Molecular Neurobiology / Klein, MPI of Neurobiology, Max Planck Society, ou_1113546              

Inhalt

einblenden:
ausblenden:
Schlagwörter: LARGE-T-ANTIGEN; CASEIN-KINASE-I; SIMIAN-VIRUS-40 DNA-REPLICATION; WILD-TYPE P53; PROTEIN-KINASE; BREAST-CANCER; BETA-CATENIN; TRANSGENIC MICE; SV40-TRANSFORMED CELLS; MUTATIONAL ANALYSISBiology;
 Zusammenfassung: Simian virus 40 (SV40) is a powerful tool to study cellular transformation in vitro, as well as tumor development and progression in vivo. Various cellular kinases, among them members of the CK1 family, play an important role in modulating the transforming activity of SV40, including the transforming activity of T-Ag, the major transforming protein of SV40, itself. Here we characterized the effects of mutant CK1 delta variants with impaired kinase activity on SV40-induced cell transformation in vitro, and on SV40-induced mammary carcinogenesis in vivo in a transgenic/bi-transgenic mouse model. CK1 delta mutants exhibited a reduced kinase activity compared to wtCK1 delta in in vitro kinase assays. Molecular modeling studies suggested that mutation N172D, located within the substrate binding region, is mainly responsible for impaired mutCK1 delta activity. When stably over-expressed in maximal transformed SV-52 cells, CK1 delta mutants induced reversion to a minimal transformed phenotype by dominant-negative interference with endogenous wtCK1 delta. To characterize the effects of CK1 delta on SV40-induced mammary carcinogenesis, we generated transgenic mice expressing mutant CK1 delta under the control of the whey acidic protein (WAP) gene promoter, and crossed them with SV40 transgenic WAP-T-antigen (WAP-T) mice. Both WAP-T mice as well as WAP-mutCK1 delta/WAP-T bi-transgenic mice developed breast cancer. However, tumor incidence was lower and life span was significantly longer in WAP-mutCK1 delta/WAP-T bi-transgenic animals. The reduced CK1 delta activity did not affect early lesion formation during tumorigenesis, suggesting that impaired CK1 delta activity reduces the probability for outgrowth of in situ carcinomas to invasive carcinomas. The different tumorigenic potential of SV40 in WAP-T and WAP-mutCK1 delta/WAP-T tumors was also reflected by a significantly different expression of various genes known to be involved in tumor progression, specifically of those involved in wnt-signaling and DNA repair. Our data show that inactivating mutations in CK1 delta impair SV40-induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo.

Details

einblenden:
ausblenden:
Sprache(n): eng - English
 Datum: 2012
 Publikationsstatus: Online veröffentlicht
 Seiten: 16
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: ISI: 000301123400093
DOI: 10.1371/journal.pone.0029709
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden:

Quelle 1

einblenden:
ausblenden:
Titel: PLOS ONE
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA : PUBLIC LIBRARY SCIENCE
Seiten: - Band / Heft: 7 (1) Artikelnummer: e29709 Start- / Endseite: [1] - [16] Identifikator: ISSN: 1932-6203