Mapping on Human and Mouse Chromosomes of the Gene for the β-Galactoside-Binding Protein, an Autocrine-Negative Growth Factor

Baldini, Antonio; Gress, Thomas M.; Patel, Ketan; Muresu, Rosella; Chiariotti, Lorenzo; Williamson, Penny; Boyd, Yvonne; Casciano, Ida; Wells, Valerie; Bruni, Carmelo B.; Mallucci, Livio; Siniscalco, M.

doi:10.1006/geno.1993.1039

Cited by 15 publications

(7 citation statements)

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“…LGALS1 has been reported to act as an autocrine negative growth factor that regulates cell proliferation (Goldstone and Lavin, 1991;Baldini et al, 1993) and to bind oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation (Paz et al, 2001). Interestingly, LGALS3 (galectin 3) was found to be significantly downregulated in our model, agreeing with published data (Andre et al, 1999) indicating a correlation of increased LGALS1 and reduced LGALS3 in breast carcinomas with metastatic propensity.…”

Section: Hsp27 Erbb2supporting

confidence: 90%

cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells

et al. 2003

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Section: Hsp27 Erbb2supporting

confidence: 90%

cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells

et al. 2003

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“…19. It was cloned in 1986 and is an autocrine regulator of cell proliferation with a role in the maintenance of G0 and in the control of G2 traverse [24,25]. It has been demonstrated that some genes promoted myeloid differentiation HL-60 cells by preventing programmed cell death [26].…”

Section: Discussionmentioning

confidence: 98%

Effects of human bone marrow stromal cell line (HFCL) on the proliferation, differentiation and apoptosis of acute myeloid leukemia cell lines U937, HL-60 and HL-60/VCR

et al. 2008

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This study investigated the effects of human bone marrow fibroblastoid stromal cell line (HFCL) on the proliferation, differentiation and chemosensitivity of acute myeloid leukemia cells (AML) in vitro coculture. By setting up coculture system of sensitive U937, HL-60 cell line and multidrug-resistant (MDR) HL-60/VCR cells in direct contact with human bone marrow fibroblastoid stromal cell line HFCL, or separated by transwell, the proliferation of AML cells cocultured with HFCL cells was inhibited, compared with AML cells alone. And NBT positive cells increased slightly. The percentage of G1 phase cells of AML cells cocultured with HFCL cells was higher than that without HFCL cells, and that of S phase cells was lower. The expression of CD11b and CD14 increased. Meanwhile HL-60 and HL-60/VCR cells treated by TPT were observed to have apoptosis characteristic morphological changes. The proportion of G0/G1 HL-60 and HL-60/VCR cells treated with TPT increased and the sub-G1 increased. The percentage of Annexin V-positive cells and apoptotic cells increased with expression of activated Caspase-3 and the reduced expression of Bcl-2. But when they were cocultured with HFCL cells, the percentage of Annexin V-positive cells and apoptotic cells decreased and sub-G1 reduced. After indirect contact with HFCL cells the expression of activated Caspase-3 decreased and the expression of Bcl-2 increased. After direct contact with HFCL cells for 96 h, the expression levels of 582 genes in HL-60 cells were up-regulated, and 1,323 genes were down-regulated at least twofold by Affymetrix GeneChip Human Genome U133 set A. The expression change in some genes, such as HL14, was confirmed by RT-PCR and northern blot. In a word, HFCL cells could inhibit the proliferation, induce the monocytic differentiation of U937, HL-60 and HL-60/VCR cells, and prevent TPT-induced apoptosis in HL-60 and HL-60/VCR cells via modulation of Bcl-2 and active Caspase-3. Many genes might take part in the influence of HFCL cells on AML cells, which may give important insights into the interaction of bone marrow stromal cells and leukemic cells.

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“…Functional inhibition of p110 by bGBP results in downregulation of PI3K activity, suppression of Ras-GTP loading, consequent loss of MAPK activation and block of cell proliferation. It is of interest to notice, within the context of bGBP as a downregulator of oncogene signalling, that by mapping on human chromosome 22q12Àq13.1 (Baldini et al, 1993), a region translocated or deleted in a number of human tumours (Aurias et al, 1984;Bridge et al, 1990;Rey et al, 1993;Turc-Carel et al, 1998), the gene encoding bGBP (Chiariotti et al, 1991) is brought to attention as a prospective tumour suppressor gene.…”

Section: Inhibition Of Pi3k By Bgbp Blocks Cell Proliferation V Wellsmentioning

confidence: 99%

Functional inhibition of PI3K by the βGBP molecule suppresses Ras–MAPK signalling to block cell proliferation

2007

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The mechanisms of signal transduction from cell surface receptors to the interior of the cell are fundamental to the understanding of the role that positive and negative growth factors play in cell physiology and in human diseases. Here, we show that a functional link between phosphatidylinositol-3-OH kinase (PI3K) and Ras is suppressed by the b-galactoside binding protein (bGBP) molecule, a cytokine and a negative cell-cycle regulator. Ras-mitogen-activated protein kinase (MAPK) signalling is blocked by bGBP owing to its ability to inhibit the p110 catalytic subunit of PI3K, whose basal activity is required for Ras activation. Functional inhibition of p110 by bGBP results in downregulation of PI3K activity, suppression of Ras-GTP loading, consequent loss of MAPK activation and block of cell proliferation. This study sheds light on the molecular mechanisms whereby bGBP can control cell proliferation and, by extension, may potentially control tumorigenesis by controlling PI3K. The Ras-mitogen-activated protein kinase (MAPK) signalling pathway plays a key role in the activation dynamics of transcriptional events required for mammalian cells to enter the cell cycle. Activation of Ras requires growth factor/receptor tyrosine kinase (RTK) interaction, RTK cross-phosphorylation leading to the formation of high-affinity binding sites for SH2 domains of the Grb2 and Shc adapter proteins, the binding of the nucleotide exchange factor SOS to the SH3 domains of Grb2 and the conversion by SOS of GDP-Ras into active GTP-Ras. The ensuing signalling cascade leads to the phosphorylation of MAPK and the activation of genes programmed to initiate cell proliferation (Downward, 2003;Mitin et al., 2005 to B5 Â 10 4 receptors/cell to control cell-cycle entry and S/G 2 traverse in normal cells Mallucci, 1991, 1992). As a cytostatic factor, bGBP induces reversible S/G 2 arrest in normal cells while activating programmed cell death in cancer cells Mallucci et al, 2003). We now report that in murine embryonic fibroblasts (MEF), chosen as a paradigm of normal cells, bGBP inhibits phosphatidylinositol-3-OH kinase (PI3K) activity, also that PI3K activity is necessary for growth factor-induced activation of Ras and that basal levels are sufficient. Comparative studies with PI3K inhibitors indicate that the p110 catalytic subunit of PI3K is a prime target of bGBP-induced signalling.To determine the mode by which bGBP inhibits cell proliferation, we have investigated mechanistic events within the signalling context that lead to the phosphorylation and activation of transcription factors involved in cell-cycle entry and cell proliferation. We found (data not shown) that in MEF from secondary culture, held in G 0 by 20 nM Hu-r-bGBP and stimulated with either 10 ng/ml platelet derived growth factor (PDGF), 10 ng/ ml epidermal growth factor (EGF), 5 ng/ml fibroblast growth factor (FGF) or 10% fetal calf serum, there was no evidence of c-fos, c-jun nor, predictably, of c-myc mRNA expression indicating that no activating signals had reached the pr...

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Mapping on Human and Mouse Chromosomes of the Gene for the β-Galactoside-Binding Protein, an Autocrine-Negative Growth Factor

Cited by 15 publications

References 0 publications

cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells

cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells

Effects of human bone marrow stromal cell line (HFCL) on the proliferation, differentiation and apoptosis of acute myeloid leukemia cell lines U937, HL-60 and HL-60/VCR

Functional inhibition of PI3K by the βGBP molecule suppresses Ras–MAPK signalling to block cell proliferation

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