Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta

Lawton, Lee N.; Bonaldo, Maria de Fátima; Jelenc, Pierre C.; Qiu, Ling; Baumes, Susan A; Marcelino, Rudy A; Jesus, Gracielle M. de; Wellington, Sandra; Knowles, James A.; Warburton, Dorothy; Brown, Stephen; Soares, Marcelo B.

doi:10.1016/s0378-1119(97)00485-x

Cited by 180 publications

(147 citation statements)

References 38 publications

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“…Exon II is 647 base pairs in length with a 3Ј untranslated region of 244 base pairs. Like ourselves, Lawton et al [4] also reported the inability of the MIC-1 cDNA to hybridize to rodent DNA species and it has been postulated that this gene may not be present in these animals.…”

Section: Genomic Organization Of Mic-1mentioning

confidence: 72%

MIC-1 is a novel TGF-β superfamily cytokine associated with macrophage activation

Fairlie

Moore

Bauskin

et al. 1999

Journal of Leukocyte Biology

236

172

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As part of a study to identify novel genes associated with macrophage activation, we have cloned a new member of the transforming growth factor ␤ (TGF-␤) superfamily designated macrophage inhibitory cytokine 1 (MIC-1). MIC-1 is synthesized as a 62-kDa intracellular protein, which, after cleavage by a furin like protease, is secreted as a 25-kDa disulfide-linked dimeric protein. Sequence analysis indicates that it does not cluster within any existing TGF-␤ families, suggesting it may be the first member of a new grouping within the TGF-␤ superfamily. Tissue Northern blots show that MIC-1 transcripts are only found abundantly in placenta, although smaller amounts are seen in a limited number of other adult and fetal tissues. MIC-1 is not expressed in resting macrophages but is induced by a number of different activation agents, including phorbol myristate acetate, interleukin 1, tumor necrosis factor ␣, and macrophage colony-stimulating factor but not by lipopolysaccharide or interferon-␥. We have hypothesized that it may be an autocrine inhibitor of macrophage activation but its major biological role is still uncertain.J. Leukoc. Biol. 65: 2-5; 1999.

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Section: Genomic Organization Of Mic-1mentioning

confidence: 72%

MIC-1 is a novel TGF-β superfamily cytokine associated with macrophage activation

Fairlie

Moore

Bauskin

et al. 1999

Journal of Leukocyte Biology

236

172

View full text Add to dashboard Cite

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“…HIF-1 is known as one of the most important transcription factors involved in oxygen homeostasis (Carmeliet et al, 1998). The analysis of the MIC-1 gene promoter revealed the presence of putative consensus sequences for several transcription factors, including AP-1 and, Sp1 and Sp3 (Baek et al, 2001a;Bottner et al, 1999;Lawton et al, 1997). AP-1 has been shown previously to act as an anoxic stress mediator in glioblastoma cell lines LN-229 and LN-Z308 (Desbaillets et al, 1999) and might be a possible candidate in anoxia mediated MIC-1 up-regulation.…”

Section: Discussionmentioning

confidence: 99%

“…The MIC-1 gene is highly expressed in placenta and in adult prostate tissue, and at lower levels in liver, kidney, pancreas, and fetal brain (Fairlie et al, 1999;Hromas et al, 1997;Lawton et al, 1997;Paralkar et al, 1998). In the brain, MIC-1 is expressed in epithelial cells of the choroid plexus and secreted into the cerebral spinal fluid (Strelau et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Anoxia induces macrophage inhibitory cytokine-1 (MIC-1) in glioblastoma cells independently of p53 and HIF-1

et al. 2002

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“…One of the genes identified encodes a 1.2-kb 1 mRNA that is strongly up-regulated by wild-type p53 and to a lesser extent by radiation treatment. Sequence analysis indicated that this gene corresponds to placental transforming growth factor-␤ (PTGF-␤) (30,31), a novel member of the transforming growth factor superfamily of proteins involved in the regulation of cell proliferation, differentiation, and apoptosis (32,33).…”

mentioning

confidence: 99%

Placental Transforming Growth Factor-β Is a Downstream Mediator of the Growth Arrest and Apoptotic Response of Tumor Cells to DNA Damage and p53 Overexpression

Li¹,

Wong²,

Ayed³

et al. 2000

Journal of Biological Chemistry

240

258

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The p53 tumor suppressor gene and members of the transforming growth factor-␤ (TGF-␤) superfamily play central roles in signaling cell cycle arrest and apoptosis (programmed cell death) in normal development and differentiation, as well as in carcinogenesis. Here we describe a distantly related member of the TGF-␤ superfamily, designated placental TGF-␤ (PTGF-␤), that is upregulated in response to both p53-dependent and -independent apoptotic signaling events arising from DNA damage in human breast cancer cells. PTGF-␤ is normally expressed in placenta and at lower levels in kidney, lung, pancreas, and muscle but could not be detected in any tumor cell line studied. The PTGF-␤ promoter is activated by p53 and contains two p53 binding site motifs. Functional studies demonstrated that one of these p53 binding sites is essential for p53-mediated PTGF-␤ promoter induction and specifically binds recombinant p53 in gel mobility shift assays. PTGF-␤ overexpression from a recombinant adenoviral vector (AdPTGF-␤) led to an 80% reduction in MDA-MB-468 breast cancer cell viability and a 50 -60% reduction in other human breast cancer cell lines studied, including MCF-7 cells, which are resistant to growth inhibition by recombinant wild-type p53. Like p53, PTGF-␤ overexpression was seen to induce both G 1 cell cycle arrest and apoptosis in breast tumor cells. These results provide the first evidence for a direct functional link between p53 and the TGF-␤ superfamily and implicate PTGF-␤ as an important intercellular mediator of p53 function and the cytostatic effects of radiation and chemotherapeutic cancer agents.

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Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta

Cited by 180 publications

References 38 publications

MIC-1 is a novel TGF-β superfamily cytokine associated with macrophage activation

MIC-1 is a novel TGF-β superfamily cytokine associated with macrophage activation

Anoxia induces macrophage inhibitory cytokine-1 (MIC-1) in glioblastoma cells independently of p53 and HIF-1

Placental Transforming Growth Factor-β Is a Downstream Mediator of the Growth Arrest and Apoptotic Response of Tumor Cells to DNA Damage and p53 Overexpression

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