Expression changes in mouse embryo fibroblasts associated with the loss of menin (menin-null)

ABSTRACT: Multiple endocrine neoplasia, type 1 (MEN1) is an autosomal dominant familial cancer syndrome characterized primarily by endocrine tumors of the parathyroids, anterior pituitary and enteropancreatic endocrine tissues. Affected individuals carry a germline loss-of-function mutation of the MEN1 gene, and tumors arise after loss of the second allele. Homozygous loss of Men1 in the germline of mice results in early embryonic lethality, with defective development of neural tube, heart, liver, and craniofacial structures. We generated immortalized Wild type (Wt) and menin-null mouse embryo fibroblast (MEF) cell lines and evaluated their characteristics, including global expression patterns. The Wt and menin-null cell lines were aneuploid, and the nulls did not display tumorigenic characteristics in soft-agar assay. Expression arrays in menin-null MEFs revealed altered expression of several extracellular matrix proteins that are critical in organogenesis. Specifically, transcripts for fibulin-2 (Fbln2), periostin (Postn) and versican (Cspg2, chondroitin sulfate proteoglycan), genes critical for the developing heart and known to be induced by TGF-beta, were decreased in their expression in menin-null MEFs. Fbln2 expression was the most affected, and the reduction in menin-null MEFs for Fbln2, Postn and Cspg2 was 16.18, 5.37 and 2.15-fold respectively. Menin-null MEFs also showed poor response to TGF-beta-induced Smad3-mediated transcription in a reporter assay, supporting a role for menin in this pathway. The expression changes associated with the loss of the tumor suppressor menin provide insights into the defective organogenesis observed during early embryonic development in Men1-null mouse embryos. Keywords: Wild type and menin-null mouse embryo fibroblasts

ORGANISM(S): Mus musculus

PROVIDER: GSE6513 | GEO | 2007/06/01

SECONDARY ACCESSION(S): PRJNA98597

REPOSITORIES: GEO