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)

The expression of mucins is important for tumor invasiveness and metastasis. In our previous report (Am. J. Respir. Crit. Care Med. 1997; 155:1419-1427), non-small cell lung cancers bearing sialomucin expression tended to relapse earlier than those without sialomucin. However, it remained unclear whether the expression of sialomucin in lung cancer is caused by an abnormal glycosylation process or by the expression of a specific mucin gene product. To address this problem, we established a modified quantitative competitive polymerase chain reaction (QC-PCR) analysis. RNA internal standards of MUC1, MUC2, and MUC5AC non-tandem repeat sequences were constructed, and known copy numbers of mucin RNA internal standards were introduced into reverse transcription-polymerase chain reactions (RT-PCR) for each mucin gene in order to compete with native mucin gene RNA during the reaction. The RNA of Gbeta-like gene (a housekeeping gene) was used as internal control for the RNA analysis. Twenty-five lung cancer tissues (13 adenocarcinomas and 12 squamous cell carcinomas) were used for analysis. Mann-Whitney rank sum test was applied to compare the expression amounts of different mucin genes in tissues. The results revealed that adenocarcinoma expressed higher amounts of MUC5AC gene than did squamous cell carcinoma (P = 0.03). The expression amount of MUC5AC correlated positively with the expression status of sialomucin (P = 0.012). Further studies are anticipated to elucidate the underlying mechanism contributing to this phenomenon.
Am J Respir Cell Mol Biol 1998 May
PMID:Quantitative analysis of mRNA encoding MUC1, MUC2, and MUC5AC genes: a correlation between specific mucin gene expression and sialomucin expression in non-small cell lung cancer. 956 34

6-[3-(1-Adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN or CD437), originally identified as a retinoic acid receptor gamma-selective retinoid, was previously shown to induce growth inhibition and apoptosis in human breast cancer cells. In this study, we investigated the role of AHPN/CD437 and its mechanism of action in human lung cancer cell lines. Our results demonstrated that AHPN/CD437 effectively inhibited lung cancer cell growth by inducing G0/G1 arrest and apoptosis, a process that is accompanied by rapid induction of c-Jun, nur77, and p21(WAF1/CIP1). In addition, we found that expression of p53 and Bcl-2 was differentially regulated by AHPN/CD437 in different lung cancer cell lines and may play a role in regulating AHPN/CD437-induced apoptotic process. On constitutive expression of the c-JunAla(63,73) protein, a dominant-negative inhibitor of c-Jun, in A549 cells, nur77 expression and apoptosis induction by AHPN/CD437 were impaired, whereas p21(WAF1/CIP1) induction and G0/G1 arrest were not affected. Furthermore, overexpression of antisense nur77 RNA in A549 and H460 lung cancer cell lines largely inhibited AHPN/CD437-induced apoptosis. Thus, expression of c-Jun and nur77 plays a critical role in AHPN/CD437-induced apoptosis. Together, our results reveal a novel pathway for retinoid-induced apoptosis and suggest that AHPN/CD437 or analogs may have a better therapeutic efficacy against lung cancer.
Mol Cell Biol 1998 Aug
PMID:Molecular determinants of AHPN (CD437)-induced growth arrest and apoptosis in human lung cancer cell lines. 967 82

The role of calcitonin, and other agonists which activate the cAMP pathway, in regulating transcription of the human parathyroid hormone-related protein (PTHrP) gene was investigated in a human lung cancer cell line (BEN). Both calcitonin and forskolin caused a 5-6-fold increase in transcription initiated from both the P1 and P3 promoters, but with no observed effect on the P2 promoter. Maximal 6-fold activation of the P1 promoter occurred at 16 h post-stimulation and effects of calcitonin were observed within the pM range. The PKC agonist, phorbol 12-myristate 13-acetate diester (PMA), did not modulate transcription initiated from the P1 promoter. The ionophore ionomycin had a small effect on transcription of the P1 promoter, and transcriptional control may involve an interaction between the cAMP and intracellular calcium second messenger pathways. Deletion mapping studies indicated that increases in transcription of the human PTHrP gene is being mediated via a CRE element situated at -3313 to -3306 upstream of the P1 promoter. Mutational analysis of this CRE element confirmed a role for this sequence in mediating the increase in transcription effected by cAMP. Consistent with these transfection studies, RT-PCR of PTHrP mRNA also indicated a significant increase in transcripts generated from the P1 promoter. Gel retardation assays utilising a fragment of the P1 promoter region, encompassing the putative CRE, determined that nuclear proteins were binding to this region. Competition binding studies with labelled probe and cold competitors determined that the binding was specific for this sequence. A wild-type CRE consensus oligonucleotide also competed for binding with this sequence.
Mol Cell Endocrinol 1998 Mar 16
PMID:Differential regulation of the parathyroid hormone-related protein gene P1 and P3 promoters by cAMP. 968 26

Human lung cancers overexpress several cell-membrane complement inhibitory proteins (CIP). These complement inhibitory proteins are membrane cofactor protein (CD46), decay-accelerating factor (DAF; CD55), and CD59 (protectin). These cell-membrane proteins have a wide normal tissue distribution, are known to protect normal host cells from homologous complement-mediated lysis, and are thought to facilitate tumor escape from immunosurveillance. To study whether proinflammatory cytokines that are involved in cancer growth can modulate cell-membrane CIP expression in lung cancer cells, we studied the effect of interleukin (IL)-1alpha, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma on two human lung cancer cell lines. ChaGo K-1 and NCI-H596 cell lines, undifferentiated carcinoma and lung adenosquamous carcinoma, respectively, were stimulated with different cytokines, and the effects of incubation time and cytokine concentration on cell-membrane CIP expression were studied. Cell-membrane CIP expression was evaluated using flow cytometry and cytokine effect was calculated as percent change in mean fluorescence intensity of each CIP molecule from its untreated control. We found that DAF was the lung cancer cell-membrane CIP molecule that was the most responsive to cytokine stimulation. Maximal stimulatory effect was usually noted 72 h after a cytokine was introduced. In ChaGo K-1 and NCI-H596 lung cancer cell lines, IL-1alpha and TNF-alpha increased DAF expression. IL-1alpha (100 U/ml/72 h) increased DAF expression up to a maximal mean of 45 and 48%, respectively, in comparison with untreated cells. TNF-alpha (1, 000 U/ml/72 h) increased DAF expression up to a mean of 131 and 46%, respectively. IFN-gamma (1 U/ml/72 h) increased DAF expression in NCI-H596 cells up to a mean of 100%, but had a slight inhibitory effect on DAF expression in ChaGo K-1 cells, decreasing expression by a mean of 17% in comparison with untreated cells. We conclude that cell-membrane DAF expression in the studied human lung cancer cell lines is modulated by IL-1alpha, TNF-alpha, and IFN-gamma, and speculate that cytokine-mediated modulation of cell-membrane DAF in human lung cancer cells might affect lung cancer cell biology.
Am J Respir Cell Mol Biol 1998 Sep
PMID:Cytokines modulate expression of cell-membrane complement inhibitory proteins in human lung cancer cell lines. 973 Aug 81

Recent reports have demostrated a link between expression of members of the family of heterogeneous nuclear ribonucleoproteins (hnRNPs) and cancer. Overexpression of hnRNP A2/B1 correlated with the eventual development of lung cancer in three different clinical cohorts. We have studied the expression of hnRNP A2/B1 messenger RNA (mRNA) and protein during mammalian development. The expression of hnRNP A2/B1 mRNA and protein are parallel but change dynamically during critical periods in mouse pulmonary development. hnRNP A2/B1 is first detected in the lung in the early pseudoglandular period, peaks at the beginning of the canalicular period, and remains high during the saccular (alveolar) period. In mouse and rat, hnRNP A2/B1 expression is first evident in the earliest lung buds. As lung development progresses, the cuboidal epithelial cells of the distal primitive alveoli show high levels of the ribonucleoprotein, which is almost undetectable in the proximal conducting airways. The expression of hnRNP A2/ B1 is restricted in mature lung. Similar dynamic pattern of expression through lung development was also found in rat and human lung. Upregulated expression of hnRNP A2/B1 at critical periods of lung development was comparable to the level of expression found in lung cancers and preneoplastic lesions and is consistent with hnRNP A2/B1 overexpression playing an oncodevelopmental role.
Am J Respir Cell Mol Biol 1998 Oct
PMID:Expression of heterogeneous nuclear ribonucleoprotein A2/B1 changes with critical stages of mammalian lung development. 976 51

Interleukin-6 (IL-6) is involved in regulation of the immune response, acute phase reaction, and cell proliferation. The aim of this study was to investigate whether IL-6 is implicated in cell proliferation of human non-small-cell lung cancer (NSCLC) cell lines. We analyzed IL-6 messenger RNA (mRNA) and protein expression in eight NSCLC cell lines: A549, Calu3, Calu6, H23, H522, H810, H1155, and H1299. The A549, Calu3, Calu6, and H23 cell lines expressed IL-6 mRNA and protein. In these cell lines, fetal calf serum (FCS) significantly increased cell proliferation as assessed by thymidine incorporation. In the presence of IL-6 antisense oligonucleotides, both proliferation and IL-6 synthesis were downregulated. In contrast, IL-6 mRNA and protein could not be detected in the NSCLC cell lines H522, H810, H1155, and H1299. In these NSCLC cell lines, FCS only marginally increased cell proliferation and IL-6 antisense oligonucleotides did not affect cell proliferation. The addition of neither exogenous IL-6 nor neutralizing anti-IL-6 antibodies affected cell proliferation in any of the experiments. Our data thus provide evidence that intracellular IL-6 is required in the control of cell proliferation in a subset of human NSCLC cell lines. We suggest the existence of two subtypes of NSCLC, an IL-6-dependent and an IL-6-independent type.
Am J Respir Cell Mol Biol 1998 Oct
PMID:Proliferation of human non-small-cell lung cancer cell lines: role of interleukin-6. 976 57

We earlier reported that TIS21 mRNA expression was markedly decreased in A549 and NCIH69 human lung cancer cells and in thymic carcinoma tissues obtained from transgenic mice containing simian virus 40 large T antigen (J Cancer Res Clin Oncol 121:279-284, 1995). To determine how TIS21 inhibits growth, we made 293 cells that constitutively expressed TIS21 protein. The constitutive TIS21 expresser lines C9 and C11 grew to a lower saturation density than did those in the vector-transfected clones (V7 and V10) and antisense-transfected clones (AS1 and AS4), and the size of the C9 and C11 cells increased significantly after transfection with TIS21 cDNA. The serum-stimulated cell cycle was analyzed by fluorescence-activated cell sorting after double thymidine treatment; V10 progressed normally through the cell division cycle, but C9 and C11 cells accumulated continuously in G1 phase until 36 h after treatment. On the other hand, the progression of cells that had already entered to S or G2/M phase was not inhibited. When cell-cycle regulatory proteins were measured, C9 and C11 cells showed significantly reduced synthesis of cyclin E and cyclin-dependent kinase (cdk) 4 as well as a decrease in cyclin E-associated cdk activity. These observations led us to conclude that TIS21 overexpression in G1 phase decreased the amounts of cyclin E and cdk4, thereby decreasing the activity of cdks at the G1-S transition.
Mol Carcinog 1998 Sep
PMID:Induction of growth inhibition of 293 cells by downregulation of the cyclin E and cyclin-dependent kinase 4 proteins due to overexpression of TIS21. 976 35

In the United States, Australia, Northern Europe, and Canada, malignant melanoma is increasing at a faster rate than any other cancer, with the exception of lung cancer in women. Major advances have been made in the molecular biology and immunology of melanoma. These advances in basic science have led to more rational approaches to specifically targeting melanoma cells, with promising results in the clinic. An increased understanding of how melanoma spreads has led to more selective, less invasive surgical procedures that do not compromise patient health. Combinations of chemotherapy and immunotherapy are now available for patients with advanced melanoma that affect both the length and quality of the patients' lives. This review of the molecular biology of melanoma development and progression discusses the disease's etiology, molecular genetics, cell-surface antigens, experimental models, biological markers, and new forms of treatment. As we continue to learn more about malignant melanoma, we will be able to devise more specific and effective treatments that will give patients with this potentially deadly disease longer and more productive lives.
Mol Carcinog 1998 Nov
PMID:Molecular biology of human melanoma development and progression. 983 74

Telomerase maintains telomere length and is considered to be necessary for the indefinite proliferation of human cells. Telomerase activity is detected not only in germline and immortal cancer cells, but also in stem/progenitor cells of renewal tissues and activated lymphocytes. While it is generally agreed that telomerase is a useful tumor marker, the utility of telomerase activity in non-cancerous cells should also be considered. In the present study, we quantitatively examined telomerase activity in 56 cytology samples and 106 bronchoalveolar lavage samples obtained from patients with various respiratory diseases. Fourteen of 34 samples obtained from lung cancer patients showed detectable telomerase activity, while only 7 of 128 samples obtained from patients without lung cancer did (p<0.001). Moreover, 12 of 14 telomerase-positive samples with lung cancer showed strong signals, while none without lung cancer did. Among 106 non-cancerous bronchoalveolar lavage samples, 4 telomerase positive samples had increased number of lymphocytes and increased disease progression. These findings indicate that evaluation of telomerase activity may not only be a useful diagnostic test for lung cancer, but may also be a marker of disease aggressiveness for immune-associated lung diseases.
Int J Mol Med 1998 Mar
PMID:Telomerase activity as a novel marker of lung cancer and immune-associated lung diseases. 985 60

Tumor necrosis factor (TNF)-alpha has been shown to induce shedding of ICAM-1. Experimental studies report that soluble intercellular adhesion molecule-1 (sICAM-1) may interfere with the host immunesurveillance system. Serum levels of TNF-alpha and sICAM-1 were determined by ELISA in 112 non-small cell lung cancer (NSCLC) patients. Serum concentration of TNF-alpha and sICAM-1 were related to tumor burden and progression; a significant correlation was observed between circulating levels of TNF-alpha and sICAM-1. Our study suggests that ICAM-1 could be a marker of TNF-alpha activity and that high levels of these molecules may have a prognostic value in lung cancer.
Int J Mol Med 1998 Mar
PMID:Increased serum levels of tumor necrosis factor-alpha are correlated to soluble intercellular adhesion molecule-1 concentrations in non-small cell lung cancer patients. 985 72


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