Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Consistent loss of DNA sequences from several regions on the short arm of human chromosome 3 has suggested that multiple tumor suppressor genes reside on chromosome 3p in various types of cancer cells. We have focused our efforts on an analysis of chromosomal band 3p21.1 since aminoacylase-1 (ACY1), which is localized to this band, has been shown to have lower levels of expression in several small cell and non-small cell lung cancer cell lines. Starting with two cosmids within 3p21.1, D3S92 and D3S93, we have isolated two separate contigs of overlapping cosmids within 3p21.1, by screening a library of 5700 chromosome 3-specific cosmid clones. Detailed restriction maps for these two contigs show that they contain multiple clusters of rare cutting restriction endonuclease sites. One contig extends for 100 kb and encompassed both ACY1 and D3S92, and the other extends about 80 kb around the D3S93 locus. Many different restriction fragments derived from these two contigs were found to be evolutionarily conserved and hybridized to distinct message transcripts. These fragments were used to identify homologous cDNAs from an adenogastric cDNA library, and several of these cDNAs were partially sequenced. We have identified five new genes from these two contigs and there is evidence to suggest that several additional genes reside within these cosmid contigs. The genes identified from 3p21.1 were then hybridized to DNA, isolated from a series of lung cancer cell lines and matched normal and tumor DNA from lung cancer patients. No alterations were detected with any of these probes, both at the DNA or RNA levels. A similar analysis with DNA fragments derived from these two genomic regions also failed to detect any alterations.
Somat Cell Mol Genet 1994 Jul
PMID:Isolation of two contigs of overlapping cosmids derived from human chromosomal band 3p21.1 and identification of 5 new 3p21.1 genes. 797 2

Protein tyrosyl phosphorylation plays an essential role in regulating cellular events such as proliferation, differentiation and oncogenesis. The recent characterization of the family of protein tyrosine phosphatases (PTPases) suggests that dephosphorylation might be a crucial event in these phenomena. One of the functions of PTPases is to reverse the effect of protein tyrosine kinases (PTKases), many of which are oncogenes, suggesting that they may act as tumor suppressors as described for HPTP gamma. In order to investigate the implication in lung cancer of HPTP beta, a receptor PTPase, we have developed a semi-quantitative method derived from primer-directed reverse transcription (RT) and subsequent polymerase chain reaction (PCR) with 32P-labelled nucleotide. We have demonstrated that the expression of HPTP beta mRNA was dramatically decreased in lung adenocarcinomas and lung malpighian carcinomas as compared to normal lung tissue. In addition, HPTP beta was not expressed in the pulmonar adenocarcinoma cell line A427, which proliferates in a deregulated way. These results suggest that the loss of expression of HPTP beta might play a role in neoplasic transformation and thus this molecule could act as a tumor suppressor factor.
Cell Mol Biol (Noisy-le-grand) 1994 Jul
PMID:Implication of a protein-tyrosine-phosphatase in human lung cancer. 798 22

We have characterized a homozygous deletion at 3p22-p21.3 found in a lung cancer cell line ACC-LC-5. Three yeast artificial chromosomes (YACs) were isolated from a YAC library by hybridization with two cosmid probes (cCI3-1994 and cCI3-1999) representing loci that were homozygously deleted in five lung cancer cell lines. Cloning both ends of the region deleted in the cell line ACC-LC-5 revealed the deletion was an interstitial deletion within the chromosomal arm. A cosmid contig map covering the entire region corresponding to the homozygous deletion was constructed by means of Southern hybridizations. From these results and analyses by pulsed-field gel electrophoresis, this interstitial deletion on chromosome 3p22-21.3 in this cell line was estimated to be nearly 800 kb long and is smallest among five cell lines containing the homozygous deletion. The cosmid clones representing this region will contribute important new resources for isolating the putative tumor suppressor gene(s) on chromosome 3p22-21.3.
Hum Mol Genet 1994 Aug
PMID:Characterization of an 800 kb region at 3p22-p21.3 that was homozygously deleted in a lung cancer cell line. 798 12

Biliary glycoprotein (BGP), a member of the carcinoembryonic antigen gene family, is a cell surface glycoprotein that has both a transmembrane domain and a cytoplasmic domain. BGPs consist of at least four isoforms (BGPa, b, c, and d) and function in vitro as Ca(2+)-dependent homotypic intercellular adhesion molecules. The mRNA expression of BGP gene was investigated in specimens of primary and metastatic cancer tissues from 15 patients with primary lung cancer (six squamous cell carcinomas, five adenocarcinomas, and four small cell carcinomas). The specimens were also compared with normal adjacent tissues of the same individuals with squamous cell carcinoma. BGP mRNA expression was increased in carcinomatous tissues of the primary site, especially in squamous cell carcinoma, but was not detected in adjacent normal tissues by Northern blot analysis or in situ hybridization. Interestingly, BGP mRNA expression was apparently decreased in metastatic lesions compared with the primary site in the six individuals with squamous cell carcinoma. Furthermore, a loss of BGPa isoform was observed by reverse transcriptase-polymerase chain reaction in four of six patients with squamous cell carcinoma. These results suggest that the reduction of BGP expression may play an important role in the process of metastasis through decreasing adhesive interactions with surrounding cells, especially in squamous cell carcinoma.
Am J Respir Cell Mol Biol 1994 Aug
PMID:Biliary glycoprotein mRNA expression is increased in primary lung cancer, especially in squamous cell carcinoma. 804 82

The clinical use of tumor necrosis factor-alpha (TNF) is constrained by tumor cell resistance and systemic toxicity. Based on observations with murine tumors, we hypothesized that induction of local TNF production by the tumor may suppress growth of human cancer cells. To evaluate this, a human TNF cDNA was transferred to human lung cancer cell lines in vitro using a retrovirus vector to produce TNF cDNA-modified cell lines secreting TNF. In vitro cell growth was similar for parental and modified cells. All cells were resistant to TNF. The in vivo tumorigenicity of parental and modified cells was compared in nude mice. Animals injected subcutaneously with parental cells uniformly developed tumors. Tumor growth was markedly less for all modified cells, and this suppression of tumor development was reversed by anti-TNF antibody administration. Animals injected with a mixture of 50% modified and 50% parental cells or parental cell tumors injected with modified cells had decreased tumor growth, demonstrating that modified cells could suppress tumorigenicity. These data suggest that TNF can induce antitumor defenses to suppress in vivo human tumor cell growth and provide a rationale for transferring the human TNF cDNA directly to malignant cells for the therapy of human lung cancer.
Am J Respir Cell Mol Biol 1994 Sep
PMID:Suppression of in vivo tumorigenicity of human lung cancer cells by retrovirus-mediated transfer of the human tumor necrosis factor-alpha cDNA. 808 65

p185HER2, the product of the c-erbB-2 or HER2 gene, is a membrane-bound tyrosine kinase that has structural similarity to the epidermal growth factor receptor. Functionally, interaction of HER2 with its ligand or p185HER2 antibodies affects the growth and differentiation of HER2-expressing breast cancer cell lines. As p185HER2 is also expressed in human lung cancers and human lung cancer cell lines, we hypothesized that these cell lines would also respond to p185HER2 antibodies. To test this hypothesis, we cultured human non-small cell lung cancer cell lines in the presence of a p185HER2 monoclonal antibody called 4D5. 4D5 inhibited the growth of p185HER2-expressing cell lines in a dose-dependent fashion. In addition, BEAS.2B, a p185HER2-nonexpressing bronchial epithelial cell line, was transfected with the HER2 cDNA, resulting in high-level p185HER2 expression, and growth of BEAS.HER2 was now inhibited by 4D5 exposure. Mechanistically, 4D5 appeared to have a weak agonist effect on the tyrosine kinase function of p185HER2, as exposure of p185HER2-expressing cell lines to 4D5 resulted in increased p185HER2 phosphorylation. Furthermore, inhibition of tyrosine kinase function with Genistein reversed the 4D5-induced growth inhibition. Therefore, 4D5 can regulate the growth of p185HER2-expressing lung cancer cell lines through agonist effects on p185HER2.
Am J Respir Cell Mol Biol 1993 Oct
PMID:Inhibition of human lung cancer cell line growth by an anti-p185HER2 antibody. 810 37

Cytokines and immune cells are likely to be involved in the control of lung metastasis. We have therefore investigated the possibility of inhibiting lung metastases by the means of interferon-gamma (IFN-gamma) aerosolizations in a murine model of lung cancer. A Lewis lung carcinoma (3LL) was inoculated in the thigh of C57BL/6 mice. Randomized groups of 10 mice each were then treated by repeated aerosols of IFN-gamma (4,000 U/mouse) of aerosols of a Hanks' solution as controls. When the animals were killed at 18 days, the number of lung metastatic nodules was significantly reduced (by 50%; P < 0.01) after IFN-gamma aerosols, compared with controls. When the primary tumor was resected at 18 days and aerosols were continued, in the absence of local recurrence, mice treated by IFN-gamma aerosols survived longer than did controls (P < 0.05). In vitro, IFN-gamma exerted no direct antitumoral effect on 3LL cells in culture. Macrophages recovered from mice receiving IFN-gamma aerosols showed a higher antiproliferative effect on 3LL cells in vitro than did controls. Nevertheless, the higher antiproliferative effect of activated macrophages seems insufficient to explain the difference of survival that we observed between IFN-gamma-treated mice and controls.
Am J Respir Cell Mol Biol 1994 Feb
PMID:Antitumoral potential of aerosolized interferon-gamma in mice bearing lung metastases. 811 Apr 75

Cyclin D1, which is suggested to have a role in G1 control during the cell cycle, is genetically linked to BCL-1 and is widely overexpressed in parathyroid, breast, and squamous cancer cells. We postulated that cyclin D1 regulation may also be important in lung cancer. Therefore, we characterized the cell cycle-dependent expression of cyclin D1 at both mRNA and protein levels in synchronized human A549 lung carcinoma cells. Monospecific anti-cyclin D1 C-terminal peptide antibodies recognized both p36cyclinD1 and an as-yet uncharacterized 45 kD protein (p45). A549 cells were synchronized with well-studied drugs. Cyclin D1 mRNA expression remained relatively constant, with less than a twofold fluctuation during the cell cycle and with a minor peak at M phase. However, the p36cyclinD1 protein fluctuated during the A549 cell cycle and was expressed at very low levels in late G1 and at the G1/S boundary, but then increased in S phase and peaked at M phase. In contrast, p45 protein was expressed at relatively high levels in late G1 and reached maximal levels at the G1/S boundary, was expressed at decreased levels in S phase, and then had disappeared by M phase. Moreover, p45 was highly expressed only in transformed alveolar epithelial cells, but not in normal rat alveolar epithelial cells or fetal rat lung fibroblasts in primary cultures. In mink Mv1Lu cells, the expression of p45 was totally blocked by transforming growth factor-beta 1 treatment or contact inhibition. p45 protein was phosphorylated on serine, threonine, and tyrosine residues in A549 cells in culture. The phosphorylation of the p45 protein was cell cycle-regulated and reached its maximal levels at G2/M phase. The p45 protein had a different peptide map from p36cyclinD1 after cleavage with N-chlorosuccinimide. Immunoprecipitation studies showed that p45 was also anti-ubiquitin immunoreactive during the cell cycle. We conclude that p36cyclinD1 and the p45 protein are differentially regulated in a cell cycle-dependent manner in A549 cells. Although p45 is antigenically related to p36cyclinD1, it is probably not a closely cyclin-related protein. We speculate that p45 may be associated with malignant transformation and may play a distinct role from p36cyclinD1 in regulation of the cell cycle in A549 cells.
Am J Respir Cell Mol Biol 1994 Apr
PMID:Cell cycle-dependent expression of cyclin D1 and a 45 kD protein in human A549 lung carcinoma cells. 813 59

The mature adult alveolar epithelial cell (AEC) is a highly differentiated phenotype that does not readily divide and exhibits numerous specialized functions. Yet, transformed AEC proliferate aggressively in certain forms of lung cancer. Normal AEC also proliferate but in a coordinated manner during embryonic growth and fetal development as well as during lung repair. Therefore, biochemical mechanisms regulating the cell cycle in AEC are clearly of fundamental significance for understanding lung development, lung injury, and cancer. Cyclin A is a protein that varies in abundance during the cell cycle and regulates critical transition points through its association with cyclin-dependent protein kinase subunits. We postulated that high expression of cyclin A might be associated with rapid proliferation in transformed AEC. We compared the expression of cyclin A mRNA and protein in primary cultures of fetal and adult rat AEC, in the E1A-T2 neonatal rat AEC, and in the malignant A549 human AEC. We used pharmacologic blockades with mimosine, aphidicolin, and nocodazole for cell cycle synchronization, which was verified by fluorescence-activated cell sorter (FACS) analysis of cellular DNA content. Transformed cells (A549 and E1A-T2) exhibited a much higher level of expression for both cyclin A mRNA and protein than did normal rat AEC. Induction of cyclin A mRNA expression in A549 human AEC and E1A-T2 rat AEC occurred in late G1, prior to the onset of S phase. Fetal and adult rat AEC and rat E1A-T2 AEC expressed two cyclin A mRNA transcripts, whereas human A549 cells in S phase and M phase expressed three cyclin A mRNA transcripts. We conclude that transformed AEC overexpress cyclin A in comparison with primary AEC cultures, while retaining cell cycle-dependent differences in cyclin A expression. We speculate that cyclin A expression is regulated both at the transcriptional and post-transcriptional levels, and that cyclin A may play a key role in the increased proliferation of transformed AEC that is associated with the pathogenesis of lung cancer.
Am J Respir Cell Mol Biol 1993 Aug
PMID:Cyclin A expression in normal and transformed alveolar epithelial cells. 833 81

Data on human lung alpha 1- and beta-adrenoceptors and the alpha 1/beta adrenergic ratio in cancer and chronic inflammatory processes are reported. The number of alpha 1-adrenergic sites markedly increased in lung cancer parenchyma, giving a ratio of alpha 1/beta binding sites of 12/1 in cancer but almost 1:1 in control specimens. The alpha 1/beta adrenergic ratio obtained both for mild and severe chronic pneumonia and tuberculosis lung parenchyma was similar to that demonstrated for normal tissue. The above findings suggest the cancer-induced enhancement in parenchymal alpha 1-adrenergic activity.
Biochem Mol Biol Int 1993 Jan
PMID:Alterations in human lung adrenergic receptors in cancer. 838 44


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