Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During protein biosynthesis, processing of the N terminus of many proteins may occur through acetylation and deacetylation. The enzyme acylpeptide hydrolase is likely involved in deacetylation of nascent peptide chains or of bioactive peptides. The related enzyme, acylase, hydrolyzes the acetyl amino acid product of the acylpeptide hydrolase reaction to acetate and a free amino acid. There is a reciprocal relationship between the substrates for these enzymes (i.e., substrates for one enzyme are competitive inhibitors for the other). In several cultured cell lines, including normal and malignant cells, the ratio of acylpeptide hydrolase to acylase enzyme activities appears to be coordinated and characteristic for a given cell type. Thus, in normal cultured lung cells, hamster ovary cells, hepatoma cells, and lymphocyte cells, nearly equal amounts of these enzymes are expressed, conducive to optimal processing of acetylated N-terminal residues. Four lines of erythroleukemic cell lines were found to express nearly twice as much acylase as acylpeptide hydrolase activity. In the Ehrlich ascites tumor cell line, where 80% of the proteins have been reported to remain acetylated at their N terminus, acylpeptide hydrolase is hardly expressed but acylase activity is not reduced. The 3p21 region of human chromosome 3, which contains the DNF15S2 locus that encodes acylpeptide hydrolase (Jones et al., Proc Natl Acad Sci USA 1991;88:2194), undergoes deletion in some carcinoma cells; the gene that encodes for the acylase is also present on region 3p of the same chromosome. We found that both acylpeptide hydrolase and acylase activities are practically absent in six small-cell lung carcinoma cell lines tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Deficiency of acylpeptide hydrolase in small-cell lung carcinoma cell lines. 132 31

The tumors of patients with lung cancers often show loss of heterozygosity (LOH) at polymorphic loci on the short arm of chromosome 3. Most examples of small-cell lung carcinoma (SCLC) cannot be examined since they are infrequently resected. Small biopsies are, however, usually available from patients with this disease. We have used the polymerase chain reaction (PCR) to study lung tumor biopsies obtained by fiberoptic bronchoscopy and assign the genotype at 11 RFLPs in 7 well-established loci on 3p. We have demonstrated LOH in some and found that biopsy samples need to contain approximately 60% content of tumor cells if LOH is to be reliably detected. One SCLC tumor that we examined has an interstitial 3p deletion proximal to the locus D3F15S2 and thus provides information useful in mapping the position of the tumor suppressor gene on 3p.
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PMID:PCR-based RFLP analysis allows genotyping of the short arm of chromosome 3 in small biopsies from patients with lung cancer. 134 75

A human genomic DNA library was screened by using conditions of reduced stringency with a bovine cDNA probe coding for the kringle domains in prothrombin in order to isolate the human prothrombin gene. Twelve positives were identified, three of which coded for prothrombin (Degen & Davie, 1987). Phage L5 was characterized in more detail because of its strong hybridization to the cDNA probe and its unique restriction map compared to the gene coding for human prothrombin. The gene in L5 was sequenced and found to code for a kringle-containing protein. A human liver cDNA library was screened by using a genomic probe from the gene in L5. cDNAs were isolated that contained sequence identical with regions in the gene in L5. Comparison of the cDNA with the gene indicated that the gene in L5 was composed of 18 exons separated by 17 intervening sequences and is 4690 bp in length. Exons ranged in size from 36 to 242 bp in length while intervening sequences ranged from 77 to 697 bp in length. The putative protein encoded by the gene in L5 contains four kringle domains followed by a serine protease-like domain. This domain structure is identical with that found in hepatocyte growth factor (HGF), although the two proteins are only about 50% identical. On the basis of the similarity of the protein encoded by L5 and HGF, we propose that the putative L5 protein be tentatively called HGF-like protein until a function is identified. The DNA sequence of the gene and cDNA and its translated amino acid sequence were compared against GenBank and NBRF databases. Sequences homologous to DNF15S1 and DNF15S2, human DNF15S2 lung mRNA, and rat acyl-peptide hydrolase were identified in exon 17 to the 3' end of the characterized sequence for the gene. From our results, it is apparent that the gene coding for human HGF-like protein is located at the DNF15S2 locus on human chromosome 3 (3p21). The gene for acyl-peptide hydrolase is 444 bp downstream of the gene coding for HGF-like protein, but on the complementary strand. The DNF15S2 locus has been proposed to code for one or more tumor suppressor genes since this locus is deleted in DNA from small cell lung carcinoma, other lung cancers, renal cell carcinoma, and von Hippel-Lindau syndrome.
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PMID:Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor. 165 21

The tumors of patients with small cell lung carcinoma (SCLC) frequently exhibit the loss of alleles at polymorphic loci on the short arm of chromosome 3. We report the genotype analysis of six SCLC patients obtained using 15 chromosome 3 probes that identified 19 restriction fragment length polymorphisms (RFLPs). Five of the six patients were reduced to homozygosity in the tumor DNA at every informative 3p locus, and thus did not serve to delineate the deletion. However, the RFLP analysis of the tumor DNA of the sixth patient demonstrated both heterozygous and hemizygous loci on 3p and allowed the definition of an interstitial deletion that extends proximal to the D3S2 locus at 3p14.2-p21 to include at least 3p13-p14. The exclusion of the D3F15S2 locus from the deleted region, observed in this patient, is an uncharacteristic feature of SCLC deletions. This deletion includes the location of D3S30 and D3S4, and thus serves to map these loci within the proximal half of chromosome 3.
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PMID:An unusually proximal deletion on the short arm of chromosome 3 in a patient with small cell lung cancer. 167 84

An 87% identity has been found between the reported cDNA sequence that encodes acylpeptide hydrolase (EC 3.4.19.1) [Mitta, M., Asada, K., Uchimura, Y., Kimizuka, F., Kato, I., Sakiyama, F. & Tsunasawa, S. (1989) J. Biochem. 106, 548-551] and a cDNA transcribed from a locus (DNF15S2) on the short arm of human chromosome 3, reported by Naylor et al. [Naylor, S.L., Marshall, A., Hensel, C., Martinez, P.F., Holley, B. & Sakaguchi, A.Y. (1989) Genomics 4, 355-361]; the DNF15S2 locus suffers deletions in small cell lung carcinoma associated with a reduction or loss of acylase activity (EC 3.5.1.14). Acylpeptide hydrolase catalyzes the hydrolysis of the terminal acetylated amino acid preferentially from small acetylated peptides. The acetylamino acid formed by acylpeptide hydrolase is further processed to acetate and a free amino acid by an acylase. The substrates for the acylpeptide hydrolase and the acylase behave in a reciprocal manner since acylpeptide hydrolase binds but does not process acetylamino acids and the acylase binds acetylpeptides but does not hydrolyze them; however, the two enzymes share the same specificity for the acyl group. These findings indicate some common functional features in the protein structures of these two enzymes. Since the gene coding for acylpeptide hydrolase is within the same region of human chromosome 3 (3p21) that codes for the acylase and deletions at this locus are also associated with a decrease in acylase activity, there is a close genetic relationship between the two enzymes. There could also be a relationship between the expression of these two enzymes and acetylated peptide growth factors in some carcinomas.
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PMID:Genetic relationship between acylpeptide hydrolase and acylase, two hydrolytic enzymes with similar binding but different catalytic specificities. 200 56

The ERBA beta gene codes for a DNA-binding thyroid hormone receptor (THR) and maps to chromosome 3p21-p25, overlapping a 3p deletion characterizing small-cell lung carcinoma (SCLC). A DNA clone detecting an RFLP at the ERBA beta locus has been used to probe a large number of lung tumors. Virtually all SCLC had lost heterozygosity, showing that the 3p deletion in SCLC includes this gene. A substantial but smaller proportion of non-small-cell carcinomas had lost heterozygosity at ERBA beta. Among all non-small-cell tumors some had lost heterozygosity at the proximal locus DNF15S2 (band 3p21) but not at ERBA beta, whereas none were found where the reverse was true. Therefore, the locus which plays a role in non-small-cell tumorigenesis probably lies closer to DNF15S2 than to ERBA beta and is almost certainly not the latter.
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PMID:Loss of heterozygosity in a gene coding for a thyroid hormone receptor in lung cancers. 253 19

All types of lung carcinoma are characterized by a high frequency of loss of sequences from the short arm of chromosome 3, the smallest region of overlap containing D3F15S2 in band p21. Here we characterize a 440-kilobase segment from this region, which we found homozygously deleted in one of our small cell lung cancer-derived cell lines. The homozygous deletion maps between UBE1L and ZnF16, just centromeric to D3F15S2. Yeast artificial chromosomes with inserts originating from the deleted region are very unstable and readily lose parts of their insert.
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PMID:A homozygous deletion in a small cell lung cancer cell line involving a 3p21 region with a marked instability in yeast artificial chromosomes. 803 51

Deletion mapping of chromosome 3p was performed on 47 cases of human uterine cervical cancer using 24 polymorphic DNA markers including five inter-Alu DNA markers and two NotI-boundary cosmid markers obtained in our laboratory. The most likely order of these 24 polymorphic DNA markers was determined as being cen-[D3S4, H8]-D3S693-D3S659-D3S30-D3S687-[D3S2, UR9, UR47]-J36-J17-GNAI2B-D3F15S2-D3S643- D3S32-D3S23-D3S686-H35-UR189-D3S685-D3S 11 - D3S12-THRB-D3S22-pter, based on the data from radiation hybrid mapping genetic linkage analysis and in situ hybridization. Loss of heterozygosity (LOH) at one or more loci on chromosome 3p was detected in 21 of 47 cases (45%). Four tumors showed partial or interstitial deletions, and the common region of LOH in these tumors was 3p13-p21.1 between the D3S30 marker and the D3S2 marker. Candidates for tumor-suppressor genes, APEH, D8, GNA12B, ZNF35, RARB, THRB and RAFI, were all mapped outside of the common region in uterine cervical cancer. However, this region is commonly deleted in carcinoma of the lung, breast and kidney, and encompasses the breakpoint of the (3;8) translocation in hereditary renal cell carcinoma. This result indicates the presence of a novel tumor-suppressor gene in the region of 3p13-p21.1, which is involved in the development of several human cancers.
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PMID:Deletion mapping of chromosome 3p in human uterine cervical cancer. 809 26