Mxi1 regulates cell proliferation through insulin-like growth factor binding protein-3.
Mxi1, a member of the Myc-Max-Mad network, is an antagonist of the c-Myc oncogene and is associated with excessive cell proliferation. Abnormal cell proliferation and tumorigenesis are observed in organs of Mxi1-/- mice. However, the Mxi1-reltaed mechanism of proliferation is unclear. The present study utilized microarray analysis using Mxi1 mouse embryonic fibroblasts (MEFs) to identify genes associated with cell proliferation. Among these genes, insulin-like growth factor binding protein-3 (IGFBP-3) was selected as a candidate gene for real-time PCR to ascertain whether IGFBP-3 expression is regulated by Mxi1. Expression of IGFBP-3 was decreased in Mxi1-/- MEFs and Mxi1-/- mice, and the gene was regulated by Mxi1 in Mxi1 MEFs. Furthermore, proliferation pathways related to IGFBP-3 were regulated in Mxi1-/- mice compared to Mxi1+/+ mice. To determine the effect of Mxi1 inactivation on the induction of cell proliferation, a proliferation assay is performed in both Mxi1 MEFs and Mxi1 mice. Cell viability was regulated by Mxi1 in Mxi1 MEFs and number of PCNA-positive cells was increased in Mxi1-/- mice compared to Mxi1+/+ mice. Moreover, the IGFBP-3 level was decreased in proliferation defect regions in Mxi1-/- mice. The results support the suggestion that inactivation of Mxi1 has a positive effect on cell proliferation by down-regulating IGFBP-3.
Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
Je Yeong
JY
Ko
Kyung Hyun
KH
Yoo
Han-Woong
HW
Lee
Jong Hoon
JH
Park
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D025521:Tumor Suppressor Proteins; C512788:Mxi1 protein, mouse