1: Biochem Biophys Res Commun. 2001 Mar;281(5):1234-40. 

Msx1 gene overexpression induces G1 phase cell arrest in human ovarian cancer
cell line OVCAR3.

Park J, Park K, Kim S, Lee JH.

National Creative Research Initiatives Center for ARS Network, Department of
Obstetrics and Gynecology, Molecular Therapy Research Center, Samsung Medical
Center, Sungkyunkwan University, 50 Ilwon-Dong, Kangnam-Ku, Seoul, 135-710,
Korea.

Recent evidence suggested an involvement of homeobox genes in tumorigenesis.
Here we investigated whether one of homeobox-containing genes, Msx1, might be
involved in the regulation of cell proliferation and cell cycle using Msx1
overexpressing human ovarian cancer cell line, OVCAR3. Overexpression of Msx1 in
OVCAR3 cells inhibited cell proliferation by markedly increasing the length of
the G1 phase of the cell cycle over control cells. Consistent with this result,
dramatic suppression of cyclins D1, D3, E, cyclin-dependent kinase 4, c-Jun, and
Rb was observed. Elevated expression of genes involved in the growth arrest and
apoptosis (GADD153 and apoptotic cystein protease MCH4) and suppression of
proliferation associated protein gene (PAG) in Msx1-overexpressing cells by cDNA
expression array analysis provide further evidence for a potential repressor
function of Msx1 in cell cycle progression. Copyright 2001 Academic Press.

PMID: 11243867 [PubMed - indexed for MEDLINE]


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2: J Biol Chem. 1999 Jul 9;274(28):19838-45. 

Id genes are direct targets of bone morphogenetic protein induction in embryonic
stem cells.

Hollnagel A, Oehlmann V, Heymer J, Ruther U, Nordheim A.

Institut fur Molekularbiologie, Medizinische Hochschule Hannover, D-30625
Hannover, Germany.

Bone morphogenetic proteins (BMPs) are morphogenetic signaling molecules
essential for embryonic patterning. To obtain molecular insight into the
influence of BMPs on morphogenesis, we searched for new genes directly activated
by BMP signaling. In vitro cultured mouse embryonic stem (ES) cells were used,
cultivated in chemically defined growth medium (CDM). CDM-cultured ES cells
responded very selectively to stimulation by various mesoderm inducers (BMP2/4,
activin A, and basic fibroblast growth factor). BMP2/4 rapidly induced
transcript levels of the homeobox genes Msx-1 and Msx-2 and the proto-oncogene
JunB, whereas c-jun transcripts displayed delayed albeit prolonged increase.
Using differential display cDNA cloning, six direct BMP target genes were
identified. These include Id3, which showed strong mRNA induction, and the
moderately induced Cyr61, DEK, and eIF4AII genes, as well as a gene encoding a
GC-binding protein. Besides Id3, also the Id1 and Id2 genes were activated by
BMP4 in both ES cells and a range of different cell lines. Id genes encode
negative regulators of basic helix-loop-helix transcription factors. In vivo we
observed local ectopic expression of Id3 and Msx-2 mRNAs in Ft/+ embryos at
overlapping regions of ectopic Bmp4 misexpression. We therefore propose that the
Msx and Id genes are direct target genes of embryonic BMP4 signaling in vivo.

PMID: 10391928 [PubMed - indexed for MEDLINE]


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