| First Author | Almholt K | Year | 2003 |
| Journal | Oncogene | Volume | 22 |
| Issue | 28 | Pages | 4389-97 |
| PubMed ID | 12853975 | Mgi Jnum | J:84633 |
| Mgi Id | MGI:2668764 | Doi | 10.1038/sj.onc.1206601 |
| Citation | Almholt K, et al. (2003) Metastasis of transgenic breast cancer in plasminogen activator inhibitor-1 gene-deficient mice. Oncogene 22(28):4389-97 |
| abstractText | The plasminogen activator inhibitor-1 (PAI-1) blocks the activation of plasmin(ogen), an extracellular protease vital to cancer invasion. PAI-1 is like the corresponding plasminogen activator uPA (urokinase-type plasminogen activator) consistently expressed in human breast cancer. Paradoxically, high levels of PAI-1 as well as uPA are equally associated with poor prognosis in cancer patients. PAI-1 is thought to play a vital role for the controlled extracellular proteolysis during tumor neovascularization. We have studied the effect of PAI-1 deficiency in a transgenic mouse model of metastasizing breast cancer. In these tumors, the expression pattern of uPA and PAI-1 resembles that of human ductal breast cancer and plasminogen is required for efficient metastasis. In a cohort of 63 transgenic mice that were either PAI-1-deficient or wild-type sibling controls, primary tumor growth and vascular density were unaffected by PAI-1 status. PAI-1 deficiency also did not significantly affect the lung metastatic burden. These results agree with the virtual lack of spontaneous phenotype in PAI-1-deficient mice and humans and may reflect that the plasminogen activation reaction is not rate limiting for tumor vascularization and metastasis, or that there is a functional redundancy between PAI-1 and other inhibitors of the uPA/plasmin system, masking the effect of PAI-1 deficiency. |
