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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In cultured, undifferentiated normal human bronchial epithelial (HBE) cells, transglutaminase activity was localized predominantly in the cytosolic fraction of cell lysates. Upon squamous differentiation, this cytosolic activity declined and was replaced by a 40-fold increase in the activity of particulate (membrane-associated) transglutaminase. Immunoblot analysis demonstrated that the cytosolic transglutaminase was Type II (tissue) transglutaminase and that squamous differentiation shifted gene expression to the Type I (epidermal) transglutaminase. Retinoic acid, an inhibitor of squamous cell differentiation, suppressed the increase in Type I transglutaminase. The decrease in Type II transglutaminase activity was unaffected by retinoic acid. Transforming growth factor-beta 1 (TGF-beta 1) enhanced Type II transglutaminase activity about 10-fold in the undifferentiated cells but did not increase Type I transglutaminase or cholesterol sulfate, two early markers of squamous differentiation. TGF-beta 2 was equivalent to TGF-beta 1 in inducing Type II transglutaminase and in inhibiting the growth of HBE cells. The differentiation-related and TGF-beta-induced changes in transglutaminase activity were reflected in the level of transglutaminase Type I and Type II protein and mRNA. Expression of transglutaminases in lung carcinoma cell lines was variable. No correlation was observed between the expression of Type I transglutaminase and the classification of the cells as squamous cell carcinoma. Several lung carcinoma cell lines exhibited high levels of Type II transglutaminase activity that were increased several-fold by TGF-beta 1 treatment. Retinoic acid was ineffective in altering transglutaminase expression in most cell lines but induced Type II transglutaminase in a time- and dose-dependent manner in NCI-HUT-460 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of type I and type II transglutaminase in normal human bronchial epithelial and lung carcinoma cells. 135 92

Imbalance in the Kb and Db region encoded molecules is observed in Lewis lung carcinoma clones. The uncloned metastatic population and the D122 high-metastatic clone show no expression of H-2Kb products, while the nonmetastatic A9 clone expresses Kb products. Twenty-nine new subclones of 3LL and A9 were analyzed for D-end and K-end membrane expression, primary growth rate and metastatic spread. We show that the imbalance in H-2Kb to H-2Db is correlated with metastatic properties of a given clone, but local tumor growth is not. A "low Kb/low Db" phenotype is nonmetastatic as is a "high Kb/high Db" phenotype; a "low Kb/high Db" is highly metastatic and a "medium Kb/high Db" is moderately metastatic. We find support for this notion of imbalance in experiments on MHC modulation by interferon and retinoic acid. Interferon increases both Kb and Db expression of A9 and D122 clones yet the net increase of Db was greater than Kb. This was associated with an increase in metastasis formation. Retinoic acid increases the expression of the Db gene product on the nonmetastatic A9, clone, without apparent changes in Kb expression. This treatment shifts the A9 to a high-metastatic phenotype. The significance of this imbalance to the tumor--host relationship is discussed.
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PMID:MHC imbalance and metastatic spread in Lewis lung carcinoma clones. 686 90

Retinoic acid (RA) is a potent inhibitor of the malignant phenotype and of tumour cell growth. We observed that in vitro RA treatment of a highly metastatic lung carcinoma cell line (C87) induced a marked reduction in the amount of the beta 4 integrin subunit. The downregulation of this adhesion molecule was assessed by immunofluorescence, immunoprecipitation, and northern analysis. In order to investigate the effects of RA on the malignant phenotype in C87 cells we performed morphological and functional analysis after RA treatment. We found that RA was able to produce marked changes in C87 cell shape, increasing the number of flat cells (90% of the total cell population), and significantly inhibiting the malignant and invasive phenotype of C87 cells. RA treatment suppressed their clonogenic potential in soft agar (control, 20 +/- 5; RA, 0), and strongly reduced their chemotactic and chemoinvasive capacity (chemotaxis: control, 231 +/- 5; RA, 28 +/- 0; chemoinvasion: control, 132 +/- 11; RA = 2 +/- 1). FACS analysis and cell count, however, indicated that RA reduced the growth of C87 cells only partially. After 72 h of treatment we observed only a 10% reduction in the S phase fraction of the cell population. Finally, the reduced lung colony-forming ability, observed after i.v. injection of RA-treated cells (lung foci/animal: RA-treated cells, 1 +/- 0.1; untreated, 8.5 +/- 0.8), further supports the conclusion that in this murine lung carcinoma cell line a marked reduction in the expression of the beta 4 integrin subunit is associated with a marked inhibition of the malignant phenotype.
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PMID:Retinoic acid negatively regulates beta 4 integrin expression and suppresses the malignant phenotype in a Lewis lung carcinoma cell line. 828 22

Vitamin A is used as a generic term for all vitamin A derivatives with retinol-like biological activity. Retinol is the main parent compound for vitamin A. It derives from carotenoids (provitamin A) and also directly from the pre-formed vitamin A contained in the diet. The term "retinoid" is a generic descriptor of compounds structurally related to vitamin A and the synthetic analogues of retinol with or without biological activity. Retinoic acid is the active cellular catabolite. Vitamin A/retinoids have been given cancer-preventive functions and subsequently used in clinical trials to reduce lung cancer incidence in high-risk individuals. The results obtained have been in contradiction with both in vivo and in vitro promising studies. It seems therefore necessary to develop a better understanding of the vitamin A/retinoids signalling pathways in the lung. With this aim, we summarise the relevant knowledge focussed on the lung.
Lung Cancer 2009 Oct
PMID:Vitamin A/retinoids signalling in the human lung. 1934 27

Lung cancer is the second leading deadly cancer in United States. In 2007, the United States reported 213,380 new lung cancer diagnoses and 160,390 deaths caused by lung cancer. Retinoic acid and retinyl esters are the oxidized and storage forms of vitamin A in the body. At low levels, they maintain many functions as hormones affecting vision, bone growth, reproduction, cellular division, and differentiation. Recent publications have found retinoid receptors to be effective therapeutic targets in some cancer cell lines and that retinoids were functional cell modulators of the RAR/RXR nuclear hormone receptors that may impact the development of lung cancer. We hypothesize that retinoic acid and retinyl esters will negatively impact the A549 lung carcinoma cell line model in vitro and that exposure to higher concentrations of retinoids will induce impairments indicative of metabolic implications seen in chronic conditions such as cancer. Citrals are specific inhibitors of retinoid metabolism and are employed to ascertain the specificity of retinoid impacts on the cell model. The aim of this study was to expose the A549 cell line model to various concentrations of retinoic acid, and Citrals (0-160 g/ml). Growth patterns of exposed cells were screened during time intervals ranging from 24-72 hours. The effects were measured through phase microscopy, cell proliferation MTT assay, FACS analysis for cell cycle parameters and western blot analyses for cyclins. Data generated from phase contrast microscopy and MTT assays showed an increased physical destruction, metabolic impairment and a decrease in the viability of A549 cell line model after 72 hours of exposure to retinoic acids and. Observations on the effects exhibited with Citrals (cis and trans vs. diethyl acetal) suggests the reversal of retinoid toxicity and a decrease in cell metabolic as well as physical destructions and positive cell proliferation. Results from FACS analysis showed modulation in the cell cycle distribution/progression upon exposure to retinoids and that Citrals did reverse these effects in the cell line model. Western blot analysis confirmed the findings obtained from testing parameters. We conclude that modulation of metabolic integrity, cell cycle distribution and cell survival through retinoids/citrals in the lung carcinoma model is promising and warrants further therapeutic investigation.
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PMID:Retinoids and citral modulated cell viability, metabolic stability, cell cycle progression and distribution in the a549 lung carcinoma cell line - biomed 2010. 2046 16

Retinoic acid transiently induced expression of high levels of epidermal growth factor receptor (EGFR) in the human non-small cell lung carcinoma cell line H460a. Scatchard analysis revealed a 40-fold increase in the expression of EGFR on the cell surface of H460a cells within 48 h of treatment with 5 mu M concentrations of retinoic acid. RNase protection and nuclear run-off assays established that increases in EGFR expression in retinoic acid-treated cells were not the result of increased promoter activity of EGFR gene, but were more likely the result of a posttranscriptional mechanism. Immune complex kinase assays demonstrated that the EGFR induced by retinoic acid was functionally active. We conclude that retinoic acid exerts its control over expression of the EGFR in H460a cells through a posttranscriptional mechanism. Moreover, elevated EGFR might play a role in the increased tumorigenic potential exhibited by retinoic acid-treated H460a cells.
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PMID:Posttranscriptional regulation of epidermal growth-factor receptor expression by retinoic Acid in a human lung epithelial-cell line. 2159 57