Regulation of urokinase plasminogen activator (uPA) activity by E-cadherin and hormones in mammary epithelial cells

Sasaki, Carl Y.; Lin, Hsingchi; Passaniti, Antonino

doi:10.1002/(sici)1097-4652(199910)181:1<1::aid-jcp1>3.0.co;2-b

Cited by 11 publications

(3 citation statements)

References 26 publications

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“…Activation of urokinase has been shown to be dependent on E-cadherin, at least at the protein level [54]. In our system, the two cell lines that have a folate-depletion-induced elevation of E-cadherin (HCEC and NCM460) are also the ones that display an increase in urokinase.…”

Section: Discussionsupporting

confidence: 91%

Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling and folate uptake in human colonic epithelial cell lines

Crott

Liu

Keyes

et al. 2008

The Journal of Nutritional Biochemistry

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Folate deficiency may affect gene expression by disrupting DNA methylation patterns or by inducing base substitution, DNA breaks, gene deletions and gene amplification. Changes in expression may explain the inverse relationship observed between folate status and risk of colorectal cancer. Three cell lines derived from the normal human colon, HCEC, NCM356 and NCM460, were grown for 32-34 days in media containing 25, 50, 75 or 150 nM folic acid, and the expression of genes involved in cell-cycle checkpoints, intracellular signaling, folate uptake and cell adhesion and migration was determined. Expression of Folate Receptor 1 was increased with decreasing media folate in all cell lines, as was p53, p21, p16 and β-catenin. With decreasing folate, the expression of both E-cadherin and SMAD-4 was decreased in NCM356. APC was elevated in NCM356 but unchanged in the other lines. No changes in global methylation were detected. A significant increase in p53 exon 7-8 strand breaks was observed with decreasing folate in NCM460 cells. The changes observed are consistent with DNA damage-induced activation of cell-cycle checkpoints and cellular adaptation to folate depletion. Folate-depletion-induced changes in the Wnt/APC pathway as well as in genes involved in cell adhesion, migration and invasion may underlie observed relationships between folate status and cancer risk.

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Section: Discussionsupporting

confidence: 91%

Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling and folate uptake in human colonic epithelial cell lines

Crott

Liu

Keyes

et al. 2008

The Journal of Nutritional Biochemistry

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“…Alternatively, steroids may decrease uPA/uPAR expression in normal cells. Normal mammary epithelial, renal cells, and macrophages had reduced uPA and uPAR expression after dexamethasone incubation (30)(31)(32).…”

Section: Discussionmentioning

confidence: 88%

Systematic Urokinase-Activated Anthrax Toxin Therapy Produces Regressions of Subcutaneous Human Non–Small Cell Lung Tumor in Athymic Nude Mice

Ortiz

Liu

et al. 2007

Cancer Research

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The novel recombinant anthrax toxin, PrAgU2/FP59, composed of the urokinase-activated protective antigen and a fusion protein of Pseudomonas exotoxin and lethal factor was tested for anti-lung cancer efficacy in an in vivo human tumor model. Male athymic nude mice (age 4-6 weeks) were inoculated s.c. with 10 million H1299 non-small cell lung cancer (NSCLC) cells in the left flank. When tumor volumes reached 200 mm 3 (6-8 days), i.p. injection of 100 ML saline or different ratios and doses of PrAgU2/FP59 in 100 ML saline were given every 3 days for four doses and an additional dose at day 29. Animals were monitored twice daily and tumor measurements were made by calipers. The maximum tolerated doses of PrAgU2/FP59 differed dependent on the ratios of PrAgU2 to FP59 over the range of 3:1 to 25:1, respectively. At tolerated doses, tumor regressions were seen in all animals. Complete histologic remission lasting 60 days occurred in 30% of animals. PrAgU2/FP59 showed dramatic anti-NSCLC efficacy and warrants further clinical development for therapy of patients with advanced NSCLC. [Cancer Res 2007;67(7):3329-36]

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“…Urinary plasminogen activator; urokinase (uPA) Rat We found such a report of the transcriptional upregulation of uPA in mammary epithelial cells by hydrocortisone and dexamethasone (47). The literature similarly confirms that corticosteroids reduce the amount of uPA mRNA in many tissues including kidney (23,41).…”

Section: Cross-species Identification Of Gre Half-sites In 5ј-regulatmentioning

confidence: 99%

Corticosteroid-regulated genes in rat kidney: mining time series array data

Almon¹,

Lai²,

DuBois³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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Kidney is a major target for adverse effects associated with corticosteroids. A microarray dataset was generated to examine changes in gene expression in rat kidney in response to methylprednisolone. Four control and 48 drug-treated animals were killed at 16 times after drug administration. Kidney RNA was used to query 52 individual Affymetrix chips, generating data for 15,967 different probe sets for each chip. Mining techniques applicable to time series data that identify drug-regulated changes in gene expression were applied. Four sequential filters eliminated probe sets that were not expressed in the tissue, not regulated by drug, or did not meet defined quality control standards. These filters eliminated 14,890 probe sets (94%) from further consideration. Application of judiciously chosen filters is an effective tool for data mining of time series datasets. The remaining data can then be further analyzed by clustering and mathematical modeling. Initial analysis of this filtered dataset identified a group of genes whose pattern of regulation was highly correlated with prototype corticosteroid enhanced genes. Twenty genes in this group, as well as selected genes exhibiting either downregulation or no regulation, were analyzed for 5′ GRE half-sites conserved across species. In general, the results support the hypothesis that the existence of conserved DNA binding sites can serve as an important adjunct to purely analytic approaches to clustering genes into groups with common mechanisms of regulation. This dataset, as well as similar datasets on liver and muscle, are available online in a format amenable to further analysis by others.

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Regulation of urokinase plasminogen activator (uPA) activity by E-cadherin and hormones in mammary epithelial cells

Cited by 11 publications

References 26 publications

Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling and folate uptake in human colonic epithelial cell lines

Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling and folate uptake in human colonic epithelial cell lines

Systematic Urokinase-Activated Anthrax Toxin Therapy Produces Regressions of Subcutaneous Human Non–Small Cell Lung Tumor in Athymic Nude Mice

Corticosteroid-regulated genes in rat kidney: mining time series array data

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