Cell adhesion protein receptors as targets for transforming growth factor-$beta; action

Ignotz, Ronald A.; Massagué, Joan

doi:10.1016/0092-8674(87)90146-2

Cited by 459 publications

(166 citation statements)

References 49 publications

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“…TGFPl modulates expression of numerous cellular genes [l-4, [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][27][28][29]. One category belongs to nuclear proteins including c-jun.…”

Section: Discussionmentioning

confidence: 99%

Cloning from a mouse osteoblastic cell line of a set of transforming‐growth‐factor‐β1‐regulated genes, one of which seems to encode a follistatin‐related polypeptide

Shibanuma¹,

Mashimo²,

Mita³

et al. 1993

European Journal of Biochemistry

248

200

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Transforming growth factor(TGF)pl is a potent inhibitor of growth in mouse osteoblastic MC3T3-El cells. To isolate genes that are induced by TGFPl, the differential screening method was adopted using a cDNA library constructed from cells treated with TGFPl for 4 h. Six independent cDNA clones were isolated (TGFP-stimulated clone, TSC-5, TSC-36, TSC-115, TSC-128, TSC-160 and TSC-161), the expression of which was increased by TGFPl-treatment with maximal expression at 6-10 h. The steady-state levels of TSC-36, TSC-128 and TSC-160 increased almost tenfold, whereas those of TSC-5, TSC-115 and TSC-161 were elevated at most threefold. From partial nucleotide sequences, TSC-160 was found to be identical to rrg (rus-recision gene, lysyl oxydase), and TSC-115 had 80% similarity with tropomyosin cDNA, whereas other genes seemed novel. Expression of TSC-36 and TSC-160 was dramatically decreased in v-Ki-ras-transformed MC3T3 cells or in transformed NIH 3T3 cells (DT), and was recovered to normal levels in a flat revcrtant (C11). A nearly full-length copy of TSC-36 cDNA was isolated, and an open reading frame indicated that it encodes a protein of 35 kDa. An antiserum was raised against the C-terminal peptide predicted from the nucleotide sequence, and a polypeptide with an approximate molecular mass of 38 kDa was detected in cultured medium of MC3T3-El cells. The amino acid sequence of TSC-36 protein was found to have some similarity with follistatin, an activin-binding protein, and a limited similarity with the secreted protein rich in cysteine (SPARC).Growth of cells is controlled both positively and negatively by various autocrine, paracrine or endocrine growth factors, and both control mechanims are essential to maintain homeostasis. Transforming growth factor 81 (TGFp1) is a potent inhibitor of growth in various types of cells, and it also affects differentiation and gene expression [l -41. Growth of some types of mesenchymal cells is stimulated by TGFP1, but we previously reported that it inhibited growth of mouse osteoblastic cells (MC3T3-El) in the late G1 phase [ 5 ] . Growth inhibition is accompanied by induction of a certain kind of genes.TGFPl has a pronounced effect on expression of many cellular gencs, with the most striking effects on extracellularmatrix-related proteins. It increases expression of genes encoding extracellular matrix proteins [6-121 as well as proteCorrespondence to K. Nose,

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“…TGFPl modulates expression of numerous cellular genes [l-4, [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][27][28][29]. One category belongs to nuclear proteins including c-jun.…”

Section: Discussionmentioning

confidence: 99%

Cloning from a mouse osteoblastic cell line of a set of transforming‐growth‐factor‐β1‐regulated genes, one of which seems to encode a follistatin‐related polypeptide

Shibanuma¹,

Mashimo²,

Mita³

et al. 1993

European Journal of Biochemistry

248

200

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“…Many studies have shown that TGF-fl up-regulates the expression of the fibril-forming collagen types, I and IlI, of fibronectin, proteoglyeans and several collagenbinding intvgrin receptors [13,[17][18][19][20]. In addition it lowers the production of matrix metailoprotoases and increases that of their inhibitors [21 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of transforming growth factors‐β on collagen type VI expression in human dermal fibroblasts

et al. 1992

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Steady-state mRNA levels and protein synthesis of collagen type V[ were determined after stimulation of human dermal flbroblasts with translbrming growth factor-p (TGFp). While there was a 227% increase in the 0t3(Vl) subunit InRNA at maximal TGF-/~ concentration, ,',l(VI) and a2(VI) subunit mRNA lcvcis remained unchanged. Concomitantly collagen type VI immune.reactive material increased up to 172% ofcontrols in cell culture medium and cell layer extracts. Regulation of 0t3(VI) gene expression is therefore critical for the control ofcollagen type VI synthesis and determines the deposition of collagen type VI heterotrimeric molecules.

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“…In epithelial cells, TGF-b stimulates the synthesis of extracellular matrix (ECM) adhesion molecules (Ignotz and Massague, 1987). TGF-b inhibits the growth and promotes the differentiation of the TGF-b-responsive human colon cancer cell line Mosser and stimulates the cellular expression and secretion of the ECM adhesion molecules fibronectin, laminin and CEA (Chakrabarty et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-β signaling

et al. 2007

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The carcinoembryonic antigen (CEAs) family consists of a large group of evolutionarily and structurally divergent glycoproteins. The transforming growth factor-b (TGF-b) signaling pathway has been implicated in the stimulation of CEA secretion in TGF-b-sensitive colon cells, thereby possibly modulating cell adhesion and differentiation. However, the specific CEAs targeted by TGF-b signaling or underlying mechanism of the expression of CEAs has not yet been clarified. In this study, we investigated the specific CEAs targeted by the TGF-b signaling pathway. In nine human gastric cancer cell lines examined, TGF-bresponsive cell lines showed positive expression of CEAs. Expression patterns of CEA proteins correlated well with the level of CEA (CEACAM5) and CEACAM6 transcripts in these cell lines, but CEACAM1 expression was not observed in all of these cells. To investigate the role of TGF-b signaling in CEA expression, we selected two TGFb unresponsive gastric cancer cell lines; SNU638 cells that contain a mutation in the TGF-b type II receptor and SNU484 cells that express low to undetectable level of the TGF-b pathway intermediate protein, Smad3. Restoration of TGF-b signaling in these cells induced expression of the CEAs and increased activity of both CEA (CEACAM5) and CEACAM6 promoters. CEA expression was observed in the epithelium of the stomach of wild-type mice, but was markedly decreased in Smad3 null mice. These findings suggest that CEA (CEACAM5) and CEACAM6 are major target genes for Smad3-mediated TGF-b signaling.

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Cell adhesion protein receptors as targets for transforming growth factor-$beta; action

Cited by 459 publications

References 49 publications

Cloning from a mouse osteoblastic cell line of a set of transforming‐growth‐factor‐β1‐regulated genes, one of which seems to encode a follistatin‐related polypeptide

Cloning from a mouse osteoblastic cell line of a set of transforming‐growth‐factor‐β1‐regulated genes, one of which seems to encode a follistatin‐related polypeptide

Effect of transforming growth factors‐β on collagen type VI expression in human dermal fibroblasts

CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-β signaling

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