Secretion of antileucoprotease from a human lung tumor cell line

Appelhans, B.; Ender, B.; Sachse, Gabriele Elke; Nikiforov, Theo T.; Appelhans, Heribert; Ébert, W.

doi:10.1016/0014-5793(87)80413-1

Cited by 14 publications

(8 citation statements)

References 26 publications

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“…The three cell lines chosen for this study, one derived from an SCLC (ACC-LC-172) and two from NSCLCs (HS-24 and PC-10), had been established and described previously. [15][16][17] ACC-LC-172 cells were maintained in RPMI1640 supplemented with 5% fetal calf serum and penicillin-streptomycin. HS-24 and PC-10 cells were maintained in RPMI1640 supplemented with 10% fetal calf serum and penicillin-streptomycin.…”

Section: Methodsmentioning

confidence: 99%

Down‐regulation of SKP2 induces apoptosis in lung‐cancer cells

et al. 2003

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-Phase kinase associated protein 2 (SKP2), a member of the F-box family, is the substrate-recognition subunit of the SCF SKP2 ubiquitin ligase complex. 1) SKP2 has been implicated in ubiquitin-mediated degradation of the cyclin-dependent kinase (CDK) inhibitor p27 KIP1 , and positively regulates the G1/S transition. [2][3][4] This molecule is also required for ubiquitination of other cell-cycle regulators including free cyclin E (non-CDK2 bound), 5) E2F1, 6) and hOrc1p. 7) SKP2 knock-out mice grow more slowly and have smaller organs than littermate controls 5) ; cells in these mutant mice contain enlarged nuclei with polyploidy and multiple centrosomes, and they show a reduced growth rate and increased apoptosis.Several lines of evidence have suggested an oncogenic role for SKP2. For example, double-transgenic mice expressing both activated N-Ras and SKP2, targeted to the T-lymphoid lineage, developed T cell lymphoma.8) Over-expression of SKP2 has been observed in transformed cells 2) and in various types of human tumors. [8][9][10][11][12][13] Expression of SKP2 correlates with the grade of malignancy in lymphomas 8) and oral squamous-cell carcinomas.11) Elevated expression of SKP2 indicates poor prognoses for patients with oral squamous-cell carcinomas 12) and gastric cancers.13) However, little is known about the mechanism of SKP2 over-expression in cancer cells or the nature of its contribution to the malignant phenotype.Earlier studies in our laboratory revealed that the 5p11-p13 region was frequently amplified in cell lines derived from small-cell lung carcinomas (SCLCs).14) We identified a probable target gene within this amplicon, SKP2, whose amplification was associated with tumorigenesis; SKP2 was amplified in 44% and over-expressed in 83% of the primary SCLC tumors we examined. Expression of SKP2 was inversely correlated with expression of p27 KIP1 , and down-regulation of the former by transfection of an antisense oligonucleotide inhibited the growth of SCLC cells in culture. Those results indicate that amplification of chromosomal DNA is one of the mechanisms capable of up-regulating SKP2, and that consequent overexpression of this gene plays an important role in the growth of SCLC cells.In the study reported here, we explored the mechanism(s) of the observed growth inhibition induced by down-regulation of SKP2. We transfected antisense oligonucleotides into three lung-cancer cell lines that had exhibited amplification and consequent over-expression of the gene, one line derived from an SCLC and two lines from non-small cell lung cancers (NSCLCs). Antisense treatment inhibited growth of all three populations. Because SKP2 promotes progression to Sphase, 2, 4) we first tested the cultures for reduction of DNA synthesis and then examined whether apoptotic processes were contributing to the decrease in growth. Our results provide the first evidence that reducing SKP2 with antisense nucleotides can directly induce apoptosis in lung-cancer cells.

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Section: Methodsmentioning

confidence: 99%

Down‐regulation of SKP2 induces apoptosis in lung‐cancer cells

et al. 2003

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“…HS-24 cells, a tumor cell line with properties of human bronchial epithelial cells, were generously provided by Dr. Thomas Muley (Thoraxklinikum, Heidelberg, Germany) (6,28,29). This cell line has been used as a model of human airway epithelial cells in the literature (1,22,25).…”

Section: Methodsmentioning

confidence: 99%

Reactive oxygen intermediates stimulate interleukin-6 production in human bronchial epithelial cells

Yoshida

Maruyama

Fujita

et al. 1999

American Journal of Physiology-Lung Cellular and Molecular Phys

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Reactive oxygen intermediates (ROIs) play an important role in the initiation and progression of lung diseases. In this study, we investigated whether ROIs were involved in the induction of interleukin (IL)-6 in human bronchial epithelial cells. We exposed normal human bronchial epithelial cells as well as a human bronchial epithelial cell line, HS-24, to ROIs. We measured the amount of IL-6 in the culture supernatants using ELISA and the IL-6 mRNA levels using RT-PCR. Superoxide anions ([Formula: see text]), but not hydrogen peroxide (H2O2), increased IL-6 production. To examine whether it is a cell type-specific mechanism of airway epithelial cells, the experiments were also performed in human lung fibroblasts, WI-38-40. In WI-38-40 cells, neither [Formula: see text] nor H2O2increased IL-6 production. In contrast, tumor necrosis factor (TNF)-α (200 U/ml) induced IL-6 at the protein and mRNA levels in both airway epithelial cells and lung fibroblasts. This cytokine-induced IL-6 production was significantly suppressed by several antioxidants, including dimethyl sulfoxide (DMSO), in airway epithelial cells. In WI-38-40 cells, DMSO was not able to suppress IL-6 production induced by TNF-α. Pretreatment with DMSO recovered the TNF-α-induced depletion of intracellular reduced glutathione in HS-24 cells. These findings indicate that oxidant stress specifically induces IL-6 production in human bronchial epithelial cells and that in these cells ROIs may be involved in IL-6 production after stimulation with cytokines such as TNF-α. Presumably, ROIs participate in the local immune response in lung diseases via IL-6 release from bronchial epithelial cells.

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“…BET-1A cells (gift of J. E. Lechner, National Cancer Institute, Bethesda, MD), a human bronchial epithelial cell line transformed by the SV40 virus, were cultured in serum-free LHC-9 medium with 25 gg/ml fungizone, 25 U/ml penicillin, and 25 Ag/ml streptomycin (all from Biofluid Inc., Rockville, MD) (11). HS-24 cells, a human bronchial carcinoma cell line (provided by W. Ebert, Thoraxklinikum, Heidelberg-Rohrbach, Germany) were cultured in RPMI 1640 with 25 mM Hepes, pH 7.4, 2 mM glutamine, 100 ,g/ml gentamicin (all from GIBCO BRL, Gaithersburg, MD), and 10% fetal bovine serum (Biofluid Inc.) (12).…”

Section: Methodsmentioning

confidence: 99%

Vulnerability of the human airway epithelium to hyperoxia. Constitutive expression of the catalase gene in human bronchial epithelial cells despite oxidant stress.

Yoo¹,

Erzurum²,

Hay³

et al. 1994

J. Clin. Invest.

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Although catalase is a major intracellular antioxidant, the expression of the human catalase gene appears to be limited in the airway epithelium, making these cells vulnerable to oxidant stress. The basis for this limited gene expression was examined by evaluation of the expression of the endogenous gene in human bronchial epithelial cells in response to hyperoxia. Hyperoxia failed to upregulate endogenous catalase gene expression, in contrast to a marked increase in expression of the heat shock protein gene. Sequence analysis of 1.7 kb of the 5'-flanking region of the human catalase gene showed features of a "housekeeping" gene (no TATA box, high GC content, multiple CCAAT boxes, and transcription start sites). Transfection of human bronchial epithelial cells with fusion genes composed of various lengths of the catalase 5'-flanking region and luciferase as a reporter gene showed low level constitutive promoter activity that did not change after exposure to hyperoxia. Importantly, using a replication-deficient recombinant adenoviral vector containing the human catalase cDNA, levels of catalase were significantly increased in human airway epithelial cells and this was associated with increased survival of the cells when exposed to hyperoxia. These observations provide a basis for understanding the sensitivity of the human airway epithelium to oxidant stress and a strategy for protecting the epithelium from such injury. (J. Clin. Invest. 1994.93:297-302.)

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Secretion of antileucoprotease from a human lung tumor cell line

Cited by 14 publications

References 26 publications

Down‐regulation of SKP2 induces apoptosis in lung‐cancer cells

Down‐regulation of SKP2 induces apoptosis in lung‐cancer cells

Reactive oxygen intermediates stimulate interleukin-6 production in human bronchial epithelial cells

Vulnerability of the human airway epithelium to hyperoxia. Constitutive expression of the catalase gene in human bronchial epithelial cells despite oxidant stress.

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