Mutational analysis of the genes encoding urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in advanced ovarian cancer

Electrophoresis
B TürkmenV Magdolen

Abstract

Evidence has accumulated that urokinase-type plasminogen activator (uPA), its inhibitor (PAI-1) and receptor (uPAR) are involved in tumor invasion and metastasis. We analyzed the DNA sequences encoding these factors to see if they are altered in the ovarian cancer cell lines OV-MZ-6, OV-MZ-19, and OVCAR-3. In the uPA-encoding cDNA derived from OV-MZ-6 cells (but not in the uPA-cDNA from OVCAR-3 and OV-MZ-19), a so-far unknown mutation was identified in codon 121, resulting in a proline to leucine exchange. This exchange creates an AluI restriction site making restriction fragment length polymorphism (RFLP) analyses possible. Previously published PAI-1 sequences pointed to a variation of amino acid 15 of the PAI-1 signal sequence representing either threonine or alanine, which was confirmed in the present study. The uPAR cDNAs of all three cell lines encoded the published wild-type sequence. In order to elucidate the possible role of the Pro121Leu exchange in uPA and the Ala/Thr variants in the signal sequence of PAI-1 in the development and/or progression of human ovarian cancer, we studied the presence of these mutants or variants in a series of 22 ovarian cancer tissues. In addition to the wild-type sequence, the Pro121Leu ex...Continue Reading

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Citations

Dec 20, 2002·Cancer Letters·Alexandre LoktionovSheila A Bingham
Nov 23, 2006·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Mark D SternlichtZena Werb
May 12, 2001·The Journal of Investigative Dermatology·E BraungartK Degitz
Oct 23, 2010·Expert Review of Molecular Diagnostics·Karin MengeleManfred Schmitt

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