Linked Life Data

21115610

Source:http://linkedlifedata.com/resource/pubmed/id/21115610

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-12-8
pubmed:abstractText
Human germ cell tumors show a strong sensitivity to genetic background similar to Dnd1(Ter/Ter) mutant mice, where testicular teratomas arise only on the 129/SvJ genetic background. The introduction of the Bax mutation onto mixed background Dnd1(Ter/Ter) mutants, where teratomas do not typically develop, resulted in a high incidence of teratomas. However, when Dnd1(Ter/Ter); Bax(-/-) double mutants were backcrossed to C57BL/6J, no tumors arose. Dnd1(Ter/Ter) germ cells show a strong downregulation of male differentiation genes including Nanos2. In susceptible strains, where teratomas initiate around E15.5-E17.5, many mutant germ cells fail to enter mitotic arrest in G0 and do not downregulate the pluripotency markers NANOG, SOX2 and OCT4. We show that DND1 directly binds a group of transcripts that encode negative regulators of the cell cycle, including p27(Kip1) and p21(Cip)(1). P27(Kip1) and P21(Cip1) protein are both significantly decreased in Dnd1(Ter/Ter) germ cells on all strain backgrounds tested, strongly suggesting that DND1 regulates mitotic arrest in male germ cells through translational regulation of cell cycle genes. Nonetheless, in C57BL/6J mutants, germ cells arrest prior to M-phase of the cell cycle and downregulate NANOG, SOX2 and OCT4. Consistent with their ability to rescue cell cycle arrest, C57BL/6J germ cells overexpress negative regulators of the cell cycle relative to 129/SvJ. This work suggests that reprogramming of pluripotency in germ cells and prevention of tumor formation requires cell cycle arrest, and that differences in the balance of cell cycle regulators between 129/SvJ and C57BL/6 might underlie differences in tumor susceptibility.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1477-9129
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
138
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23-32
pubmed:dateRevised
2011-5-18
pubmed:meshHeading
pubmed-meshheading:21115610-3T3 Cells, pubmed-meshheading:21115610-Animals, pubmed-meshheading:21115610-Blotting, Western, pubmed-meshheading:21115610-Cadherins, pubmed-meshheading:21115610-Cell Cycle, pubmed-meshheading:21115610-Cell Differentiation, pubmed-meshheading:21115610-Germ Cells, pubmed-meshheading:21115610-Homeodomain Proteins, pubmed-meshheading:21115610-Immunohistochemistry, pubmed-meshheading:21115610-Immunoprecipitation, pubmed-meshheading:21115610-Male, pubmed-meshheading:21115610-Mice, pubmed-meshheading:21115610-Mice, Mutant Strains, pubmed-meshheading:21115610-Neoplasm Proteins, pubmed-meshheading:21115610-Nuclear Proteins, pubmed-meshheading:21115610-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:21115610-Proteins, pubmed-meshheading:21115610-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21115610-SOXB1 Transcription Factors, pubmed-meshheading:21115610-Teratoma
pubmed:year
2011
pubmed:articleTitle
Regulation of male germ cell cycle arrest and differentiation by DND1 is modulated by genetic background.
pubmed:affiliation
Department of Cell Biology, Duke University, Durham, NC 27710, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural