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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-8-13
pubmed:abstractText
Growth differentiation factor 15 (GDF15), a transforming growth factor (TGF)-beta superfamily member, has been cloned from a placenta cDNA library as a gene product that has promoted activation of pro-matrix metalloproteinase (MMP)2 mediated by membrane type (MT)1-MMP. Expression of MT1-MMP in HEK293T cells caused cleavage of the GDF15 mature form at N(252)-M(253) to produce a 6-kDa C-terminal fragment. Treatment of MCF7 cells with GDF15 induced activation of p53 and enhanced expression of p21, which was abrogated by MT1-MMP expression. GDF15 mRNA synthesis was also shown to be induced by treatment of cells with GDF15. Treatment of MCF7 cells with GDF15 caused suppression of cell proliferation. However, proliferation of MCF7 cells transfected with the MT1-MMP gene was not affected by GDF15 treatment, but was suppressed in the presence of the MMP inhibitor BB94. HT1080 cells transfected with the GDF15 gene, which endogenously express MT1-MMP, synthesize a high-level GDF15 precursor form and a low-level mature form, and treatment of cells with BB94 enhanced production of the GDF15 mature form. Consistent with GDF15 production, HT1080 cells transfected with the GDF15 gene proliferated almost equally with control cells, and addition of BB94 effectively suppressed growth of HT1080 cells transfected with the GDF15 gene concomitant with the accumulation of the GDF15 mature form, but not control cells. These results suggest that MT1-MMP contributes to tumor cell proliferation through the cleavage of GDF15, which down-regulates cell proliferation by inducing activation of p53 and p21 synthesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1347-9032
pubmed:author
pubmed:issnType
Print
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1330-5
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Cleavage of growth differentiation factor 15 (GDF15) by membrane type 1-matrix metalloproteinase abrogates GDF15-mediated suppression of tumor cell growth.
pubmed:affiliation
Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.
pubmed:publicationType
Journal Article