Monoallelic Loss of the Imprinted Gene Promotes Tumor Formation in Irradiated Mice

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Cancer-causing mutations typically involve either allele inherited from parents, and the parental source of a mutant allele is not known to influence the cancer phenotype. Imprinted genes are a class of genes whose expression is determined by a specific parental allele, either maternally or paternally derived. Thus, in contrast to most genes, the pattern of inheritance (maternal or paternal-derived) strongly influences the expression of an imprinted gene. Furthermore, imprinted genes can be differentially expressed in different tissue types. This work identifies a novel link between cancer and Grb10, an imprinted gene involved in organismal metabolism and growth. In our mouse model of radiation-induced tumors, we found monoallelic Grb10 gene loss involving the parental allele responsible for protein expression. Tumors harboring genetic loss of the expressed Grb10 allele showed absent transcript and total protein levels, despite an intact remaining wildtype Grb10 allele identified by sequencing. When restored, Grb10 suppressed tumor growth by down-regulating Ras signaling. This work demonstrates a new role for an imprinted gene in tumor formation, and shows that Grb10 functions to negatively regulate Ras signaling and suppress hyperproliferation.

Vyšlo v časopise: Monoallelic Loss of the Imprinted Gene Promotes Tumor Formation in Irradiated Mice. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005235
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005235

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