Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: HUMANGGP:031995 (CXCL1)
 2,264 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the work described here we demonstrate that the clonal cell line Mel-a-6, produced by transfection of mouse Melan-a cells with human MGSA, had an increased ability to form large colonies in soft agar and increased ability to form tumors when injected into nude mice as compared to cells transfected with the neomycin resistance gene alone. This effect appeared to be dependent on the levels of MGSA produced since another transfected clone, Mel-a-l, produced only a low level of MGSA transgene mRNA, formed only minimal large colonies in soft agar and had a tumorigenic rate equal to that of neomycin resistant controls. The histology of the Mel-a-6 tumors is compatible with features normally exhibited by melanoma tumors. The cells do not stain for melanin, and they are positive for the neural crest marker protein S-100 as well as the HMB 45 melanoma specific antigen. Immunohistochemical studies revealed expression of the human MGSA in tumor cells from tissues, excised from animals injected with cells from clone Mel-a-6. Whereas DNA ploidy analysis suggests that in vitro the Mel-a parent cell line, control Mel-a-neo, Mel-a-1 and Mel-a-6 cells show no evidence of aneuploidy, the nuclei isolated from the tumors from animals injected with Mel-a-6 do exhibit aneuploidy. These data suggest that over-expression of MGSA in immortalized melanocytes contributes to transformation.
 ...
PMID:Effects of MGSA/GRO alpha on melanocyte transformation. 186 61

BALB/MK (MK) is a continuous murine keratinocyte line whose cells are strictly dependent on exogenous epidermal growth factor (EGF) for growth in culture. A derivative cell, KC, resulted from Kirsten murine sarcoma virus transformation, and these cells no longer require EGF for their growth. Despite differences in MK and KC growth conditions, both cell lines are growth inhibited by picomolar concentrations of transforming growth factor-beta (TGF-beta). When MK and KC cells were maintained in the presence of TGF-beta, resistant variants eventually proliferated only from the KC population. In an attempt to determine the mechanism of development of TGF-beta resistance, the TGF-beta-resistant cells (KCR cells) were compared with TGF-beta-sensitive KC cells with regard to growth properties, TGF-beta 1 binding characteristics, and gene expression. KCR cells continued to synthesize DNA and proliferated in the presence of TGF-beta 1 concentrations up to 2 nM, which was 500-fold greater than the ED50 for the sensitive cells. Although the KCR cells possess similar receptor numbers and affinity for TGF-beta 1, we observed differences in affinity cross-linking studies. The KCR cells expressed more of the type III, high molecular weight cell surface binding protein and less of the type II than the KC cells. The type I moiety was clearly altered to a smaller size in some, but not all, KCR cells. In gene regulation studies, there was no apparent difference in c-Ki-ras and v-Ki-ras mRNA levels in the KC and KCR cells. Additionally, expression of TGF-alpha and TGF-beta 1 mRNA was similar in MK, KC, and KCR cells. The expression of proliferation-associated genes, such as c-myc and MGSA/c-gro/kc, which were markedly decreased by TGF-beta 1 in the MK and KC cells, was not altered by TGF-beta 1 in the KCR cells. The data suggest that the loss of TGF-beta 1 responsiveness in the KCR cells was due to an alteration in the TGF-beta receptor that did not permit signal transduction, although the existence of postreceptor alterations cannot be excluded.
 ...
PMID:Isolation and characterization of Kirsten murine sarcoma virus-transformed mouse keratinocytes resistant to transforming growth factor beta. 215 56

Microheterogeneity of connective tissue activation peptide III (CTAP-III) was revealed by preparative and analytical isoelectric focusing. Proteolytic activities in human platelet preparations resulted in four cleavage products of platelet-derived CTAP-III. Three isoforms (CTAP-III des 1-13, des 1-14, and des 1-15/NAP-2) stimulate [14C]glycosaminoglycan synthesis; two isoforms also promote [3H]DNA synthesis in human fibroblast cultures. Elastase (from porcine pancreas) cleavage of human platelet-derived CTAP-III and rCTAP-III-Leu-21 to the des 1-15 isoforms was associated with either preservation of specific anabolic biologic activity or an actual increase in specific activity. Nonenzymatic glycosylation of lysyl residues and deamination of the NH2-terminal asparagine of platelet-derived CTAP-III were commonly present, but did not correlate with the biologic activities that were measured. Protein sequence homology shows CTAP-III and its isoforms to be members of a family of proteins (including NAP-1/II-8, MGSA, and platelet factor-4) known to be associated with growth, wound repair, inflammation, and neoplasia. The consequences of proteolytic processing reported here for CTAP-III may be characteristic of the other proteins in this group.
 ...
PMID:Connective tissue activation. XXXIV: Effects of proteolytic processing on the biologic activities of CTAP-III. 221 61

The product of the human GRO gene is a cytokine with inflammatory and growth-regulatory properties; GRO is also called MGSA for melanoma growth-stimulatory activity. We have identified two additional genes, GRO beta and GRO gamma, that share 90% and 86% identity at the deduced amino acid level with the original GRO alpha isolate. One amino acid substitution of proline in GRO alpha by leucine in GRO beta and GRO gamma leads to a large predicted change in protein conformation. Significant differences also exist in the 3' untranslated region, including different numbers of ATTTA repeats associated with mRNA instability. A 122-base-pair region in the 3' region is conserved among the three GRO genes, and a part of it is also conserved in the Chinese hamster genome, suggesting a role in regulation. DNA hybridization with oligonucleotide probes and partial sequence analysis of the genomic clones confirm that the three forms are derived from related but different genes. Only one chromosomal locus has been identified, at 4q21, by using a GRO alpha cDNA clone that hybridized to all three genes. Expression studies reveal tissue-specific regulation as well as regulation by specific inducing agents, including interleukin 1, tumor necrosis factor, phorbol 12-myristate 13-acetate, and lipopolysaccharide.
 ...
PMID:Identification of three related human GRO genes encoding cytokine functions. 221 7

Expression of the chemokine MGSA/GRO is upregulated as melanocytes progress to melanoma cells. We demonstrate that constitutive and cytokine induced MGSA/GRO alpha expression requires multiple DNA regulatory regions between positions -143 to -62. We have previously shown that the NF-kappa B element at -83 to -65 is essential for basal and cytokine induced MGSA/GRO alpha promoter activity in the Hs294T melanoma and normal retinal pigment epithelial (RPE) cells, respectively. Here, we have determined that the Sp1 binding element located approximately 42 base pairs upstream from the NF-kappa B element binds Sp1 and Sp3 constitutively and this element is necessary for basal MGSA/GRO alpha promoter activity. We demonstrate that the high mobility group proteins HMGI(Y) recognize the AT-rich motif nested within the NF-kappa B element in the MGSA/GRO alpha promoter. Loss of either NF-kappa B or HMGI(Y) complex binding by selected point mutations in the NF-kappa B element results in decreased basal and cytokine induced MGSA/GRO alpha promoter activity. Thus, these results indicate that transcriptional regulation of the chemokine MGSA/GRO alpha requires at least three transcription factors: Sp1, NF-kappa B and HMGI(Y).
 ...
PMID:HMGI(Y) and Sp1 in addition to NF-kappa B regulate transcription of the MGSA/GRO alpha gene. 747 86

We demonstrate that blockage of EGF receptor signal transduction is sufficient by itself to cause a rapid, efficient, and reversible G0-like growth arrest of normal human mammary epithelial cells (HMEC) of finite lifespan as well as two immortally transformed cell lines derived from normal HMEC following in vitro transformation with benzo[a]pyrene. For normal HMEC, the significant level of endogenous production of TGF alpha requires utilization of blocking antibodies to the EGF receptor to achieve cessation of growth in mass culture, whereas removal of EGF is sufficient to arrest the immortal cell lines. In the growth-arrested cells, protein synthesis remains depressed; reexposure to EGF leads to a rapid increase in protein synthesis. Inhibition of DNA synthesis is not detectable until approximately 12 h after removal of EGF/TGF alpha and is pronounced by 24 h. Reexposure to EGF produces high levels of synthesis of the early response genes, c-myc, c-fos, c-jun, and MGSA, within 1 h. DNA synthesis increases only after 10 h, with a sharp peak after 15-20 h. Reexposure of the growth-arrested normal HMEC for 1 h with EGF allows a majority of the cells capable of cycling to subsequently enter the S phase. Little is currently known about cell cycle control in normal human epithelial cells. The efficient and gentle method of achieving reversible G0 growth arrest reported here may facilitate studies on the cell cycle of this cell type. Additionally, results from normal HMEC can be compared with those from syngeneic immortalized cell populations to determine possible cell cycle parameters altered as a result of immortal transformation.
 ...
PMID:Blockage of EGF receptor signal transduction causes reversible arrest of normal and immortal human mammary epithelial cells with synchronous reentry into the cell cycle. 768 75

The FITC-labeled C-terminal alpha-helix portion of human MGSA/gro alpha (MGSA 47-71) was shown, using flow cytometry, to bind to human melanoma cells Hs294t but not to non-melanoma cells. MGSA (47-71) is capable to induce specifically DNA synthesis of melanoma cells. These results indicate that the C-terminal portion of human MGSA is sufficient for its biological activity, thus raising questions about the importance of dimerization and of the N-terminal ELR box of the molecule which has been proposed.
 ...
PMID:Cell-binding and growth-stimulating activities of the C-terminal part of human MGSA/Gro alpha. 782 2

KC, the product of an immediate early gene induced in mouse fibroblasts by platelet-derived growth factor, was synthesized as a recombinant protein in Escherichia coli and binds with 0.8 nM affinity to mouse neutrophils. Human neutrophils also bind recombinant KC at a site competitive with human interleukin (IL8) and Gro-alpha/MGSA, consistent with binding at the IL8 type B receptor (IL8RB). The cDNA corresponding to human IL8RB hybridizes strongly with two restriction fragments in murine genomic DNA, representing candidate receptor genes for KC. Molecular cloning of both mouse genomic DNA and neutrophil exudate cell cDNA libraries yielded a receptor with approximately 68% sequence identity to both the human IL8 type A and B receptors. Transient expression of the murine receptor cDNA in COS cells conferred binding ability to KC and a related gene product, macrophage inflammatory protein-2 (MIP-2) with high affinity (approximately 5 nM). Human IL8 was a poor agonist for this expressed receptor (Kd = approximately 400 nM). The potent activity of human IL8 on mouse polymorphonuclear neutrophils is not consistent with binding on the cloned receptor and suggests that murine homologues of IL8 and an IL8 type A receptor remain to be identified. Our data indicate that KC is the murine homologue of human Gro-alpha, and the KC receptor is an IL8 type B receptor homologue capable of binding both KC and macrophage inflammatory protein-2 with high affinity.
 ...
PMID:The murine interleukin 8 type B receptor homologue and its ligands. Expression and biological characterization. 796 9

The expression of the CXC chemokine MGSA is often deregulated during viral infection, chronic inflammation, and melanoma tumor progression. In Hs294T melanoma cells, the increased constitutive expression of MGSA is due to increased gene transcription. Moreover, nuclear extracts from unstimulated Hs294T cells contain 19-fold more immunoreactive NF-kappaB p65 than that observed in normal retinal pigment epithelial (ARPE) cells. This increase in NF-kappaB p65 correlates with increased NF-kappaB DNA binding activity in Hs294T nuclear extracts. After stimulation with interleukin 1, Western and electrophoretic mobility shift assay analysis indicate that in both cell types, additional activated NF-kappaB p65 is translocated to the nucleus. However, the rate of postinduction repression of NF-kappaB DNA binding is delayed in Hs294T melanoma cells compared to ARPE cells. Western analysis of whole-cell lysates from both Hs294T and ARPE cells indicates that protein levels of the inhibitor of NF-kappaB, I-kappaB alpha, are 3-fold lower in Hs294T cells. The decrease in I-kappaB alpha cannot be attributed to alterations in the transcription or translation of I-kappaB alpha. Rather, the posttranslational processing has been altered. In Hs294T cells, the half-life of the I-kappaB alpha protein is 45 min, compared to 120 min in ARPE cells. These results indicate that in Hs294T melanoma cells the equilibrium between I-kappaB alpha degradation and resynthesis has been altered, leading to constitutive nuclear translocation and activation of NF-kappaB. Similar mechanisms could also operate in other tumorigenic processes, as well as in viral and chronic inflammatory disorders, to produce high constitutive and unregulated chemokine expression.
 ...
PMID:Enhanced degradation of I-kappaB alpha contributes to endogenous activation of NF-kappaB in Hs294T melanoma cells. 923 Feb 19

Three linked genes for the CXC-chemokine melanoma growth stimulatory activity/growth related protein (MGSA/GRO) have been previously characterized and mapped to chromosome 4q12-q13. We have isolated and characterized a pseudogene, MGSA/GRO delta, which is 83% similar to the MGSA/GRO alpha gene in the region spanning the 5' UTR, first and second exons, and the first intron. The 5' upstream sequence for the MGSA/GRO delta gene, which is also very similar to the MGSA/GRO alpha, beta, gamma genes, contains a conserved NF-kappa B motif, a TATA box, and a transcription initiation site. However, the sequence becomes markedly divergent after the second exon and hybridization studies indicate that sequences similar to the third and forth exons of other MGSA/GRO genes are not present in this gene. Additional sequence differences include alteration of the MGSA/GRO delta translation initiation codon and a one base insertion resulting in an apparent frame shift and early termination within exon 2. Multiple mutations such as these are characteristic of pseudogenes.
DNA Seq 1997
PMID:Identification and characterization of an MGSA/GRO pseudogene. 952 20


1 2 3 4 5 6 7 8 9 10 Next >>