Enhanced stability of urokinase-type plasminogen activator mRNA in metastatic breast cancer MDA-MB-231 cells and LLC-PK1 cells down-regulated for protein kinase C--correlation with cytoplasmic heterogeneous nuclear ribonucleoprotein C.

Abstract

In LLC-PK1 cells, urokinase-type plasminogen activator (uPA) mRNA has a short half-life of 70 min. We have previously demonstrated that most of the regulatory regions responsible for the rapid turnover of uPA mRNA in LLC-PK1 cells reside in its 3' untranslated region (3' UTR), where there are at least three regulatory sites, one of which is A+U-rich. This A+U-rich sequence mediates uPA mRNA stabilization induced by protein kinase C (PKC) down-regulation. In this work, we found that uPA mRNA is rather stable in MDA-MB-231 cells with a half-life of 17 h. We compared the stability of hybrid globin mRNA containing different parts of uPA mRNA in its 3' UTR and found that the A+U-rich sequence of uPA mRNA renders otherwise stable globin mRNA unstable in LLC-PK1 cells but not in MDA-MB-231 cells. We identified a cytoplasmic protein of 40 kDa (p40) which specifically interacts with the A+U-rich sequence. Levels of p40 activity as detected by ultraviolet cross-linking were higher in MDA-MB-231 and PKC-down-regulated LLC-PK1 cells than in untreated LLC-PK1 cells. Prior treatment of the cytoplasm with a specific antibody against heterogeneous nuclear ribonucleoprotein C (hnRNP C) significantly reduced p40 activity. These results suggest a correlation between the A+U-rich sequence-dependent uPA mRNA stabilization in vivo and the binding of hnRNP C to the A+U-rich sequence in vitro.

• Authors: R Nanbu, L Montero, D D'Orazio, Y Nagamine
• Journal: European journal of biochemistry (Eur J Biochem) Vol. 247 Issue 1 Pg. 169-74 (Jul 01 1997) ISSN: 0014-2956 [Print] England
• PMID: 9249023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Heterogeneous-Nuclear Ribonucleoprotein Group C
• Heterogeneous-Nuclear Ribonucleoproteins
• RNA, Messenger
• RNA-Binding Proteins
• Ribonucleoproteins
• Protein Kinase C
• Urokinase-Type Plasminogen Activator

Topics

• Animals
• Breast Neoplasms (enzymology)
• Cytoplasm (chemistry)
• Down-Regulation
• Female
• Heterogeneous-Nuclear Ribonucleoprotein Group C
• Heterogeneous-Nuclear Ribonucleoproteins
• Humans
• Kidney (enzymology)
• LLC-PK1 Cells
• Neoplasm Metastasis
• Phosphorylation
• Protein Kinase C (physiology)
• RNA, Messenger (chemistry, metabolism)
• RNA-Binding Proteins (metabolism)
• Ribonucleoproteins (analysis, physiology)
• Swine
• Tumor Cells, Cultured
• Urokinase-Type Plasminogen Activator (genetics)