Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human p53 mutant, p53Val-138 (amino acid 138, Alanine-->Valine), generated by in vitro mutagenesis was introduced into Saos-2 human osteosarcoma and Jurkat acute T-lymphoblastic leukemia cell lines, both lacking p53 protein expression. p53Val-138 caused growth arrest in Saos-2 cell line and apoptosis in Jurkat cell line at 32.5 degrees C while it allowed both cell lines to grow continuously at 37.5 degrees C. p53Val-138 activated expression of p53-responsive genes including MDM2, GADD45 and WAF1/CIP1/SD11 in Saos-2 cell line upon the temperature shift-down from 37.5 degrees C to 32.5 degrees C. Thus, p53Val-138 acted as a temperature-sensitive p53 mutant. Taking advantage of these human cell systems, we demonstrated that p53-mediated cell cycle arrest occurred in G1 and G2/M phases of Saos-2 cell line but not in Jurkat cell line. The induced level of WAF1/CIP1/SDI1 mRNA by p53 was extremely lower in Jurkat cell line than that of Saos-2 cell line. However, MDM2 mRNA accumulated to the similar levels in these two cell lines. These results suggest that a factor(s) other than p53 may be involved in differential expression of WAF1/CIP1/SDI1 and MDM2 mRNA.
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PMID:A human temperature-sensitive p53 mutant p53Val-138: modulation of the cell cycle, viability and expression of p53-responsive genes. 762 16

A series of conformationally-restricted analogues of hPTH was prepared, based on the parent peptide agonist, cyclo(Lys(18)-Asp(22))[Ala(1),Nle(8),Lys(18),Asp(22),Leu(27)]hPTH(1-31)NH(2) (2, EC(50)=0.29nM). Truncation of 2 at either the N- or C-termini resulted in peptides with reduced agonist activity as measured by stimulation of adenylate cyclase activity in the rat osteosarcoma cell line (ROS 17/2.8). Alanine- and glycine-scanning at the N-terminus of 2 was consistent with data previously obtained on linear hPTH(1-34). Other locations within the primary sequence of hPTH(1-31)NH(2) were evaluated by the placement of the [i, i+4] lactam constraining element. Ring size and lactam orientations at the 18-22 positions were also examined.
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PMID:Analogues of human parathyroid hormone (1-31)NH(2): further evaluation of the effect of conformational constraint on biological activity. 1181 62

The hSEP1 gene is the human homolog of yeast SEP1. Yeast SEP1 is a multifunctional gene that regulates a variety of nuclear and cytoplasmic functions including homologous recombination, meiosis, telomere maintenance, RNA metabolism and microtubule assembly. The function of hSEP1 is not known. We show loss or reduced expression of hSEP1 messenger RNA (mRNA) in three of four primary osteogenic sarcoma (OGS)-derived cell lines and in eight of nine OGS biopsy specimen. In addition, we find a heterozygous missense mutation (Valine(1484)>Alanine) at a conserved amino acid in the primary OGS-derived cell line U2OS. Importantly, we identified a homozygous missense mutation involving a CG-dinucleotide leading to a change in a conserved amino acid, aspartic acid(1137) >asparagine, in the primary OGS-derived cell line, TE85. hSEP1 mRNA expression was nearly undetectable in TE85 and low in U2OS cell lines. None of these mutations were identified in 20 normal samples consisting of bone, cartilage and fibroblast. The hSEP1 gene is located in chromosome 3 at 3q25-26.1 between markers D3S1309 and D3S1569. An adjacent locus defined by the polymorphic markers D3S1212 and D3S1245 has previously been reported to undergo loss of heterozygosity (LOH) at a >70% frequency in OGS and claimed to harbor an important tumor suppressor gene in osteosarcoma. The homozygous mutation in the hSEP1 mRNA in TE85 cell line suggest that this gene itself is subject to LOH. Taken together, these results suggest that hSEP1 acts as a tumor suppressor gene in OGS.
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PMID:The human homolog of yeast SEP1 is a novel candidate tumor suppressor gene in osteogenic sarcoma. 1242