PMC:4135037 / 13046-14254 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4135037","sourcedb":"PMC","sourceid":"4135037","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4135037","text":"It is well established that endocrine tumors that arise in MEN1+/− humans and Men1+/− mice exhibit LOH 3, 4, which is consistent with the classical “two-hit” model of tumorigenesis operative with inactivation of tumor suppressor genes 26. In order to determine whether Cdk2 or Cdk4 deficiency had a differential impact on Men1 LOH, we examined whether LOH had occurred at the Men1 locus in pituitary tissues and tumors from Men1+/− mice with Cdk4−/−, Cdk2−/− and Cdk-wild type backgrounds. Genomic PCR analyses unambiguously indicated that pituicytes in Men1+/−; Cdk wild-type mice and Men1+/−; Cdk2−/− mice underwent LOH, i.e., the loss of the wild-type Men1 allele in genomic DNA, while livers from those mice as non-tumorigenic control tissues retained both wild-type and mutant alleles (Fig. 4, compare lanes 4, 8 to lanes 3, 7). In contrast, pituitary tissues from Men1+/−; Cdk4−/− mice showed no sign of LOH (Fig. 4, lane 6). These results suggest that Cdk4 deficiency impedes early tumorigenic changes in Men1+/− pituicytes that normally occur in prior to the complete loss of menin expression. In contrast, Cdk2 deficiency does not alter LOH that occurs as part of the multi-step tumorigenic process.","tracks":[{"project":"2_test","denotations":[{"id":"24531709-11158604-79171868","span":{"begin":103,"end":104},"obj":"11158604"},{"id":"24531709-11158604-79171868","span":{"begin":103,"end":104},"obj":"11158604"},{"id":"24531709-12819299-79171869","span":{"begin":106,"end":107},"obj":"12819299"},{"id":"24531709-12819299-79171869","span":{"begin":106,"end":107},"obj":"12819299"},{"id":"24531709-11549677-79171870","span":{"begin":235,"end":237},"obj":"11549677"},{"id":"24531709-11549677-79171870","span":{"begin":235,"end":237},"obj":"11549677"}],"attributes":[{"subj":"24531709-11158604-79171868","pred":"source","obj":"2_test"},{"subj":"24531709-11158604-79171868","pred":"source","obj":"2_test"},{"subj":"24531709-12819299-79171869","pred":"source","obj":"2_test"},{"subj":"24531709-12819299-79171869","pred":"source","obj":"2_test"},{"subj":"24531709-11549677-79171870","pred":"source","obj":"2_test"},{"subj":"24531709-11549677-79171870","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#e793ec","default":true}]}]}}