This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dubeau, L. Articles by Laug, W. E. Search for Related Content PubMed PubMed Citation Articles by Dubeau, L. Articles by Laug, W. E.

Differential Regulation of Plasminogen Activators by Epidermal Growth Factor in Normal and Neoplastic Human Urothelium¹

Urological Cancer Research Laboratory, USC Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033 [L. D., P. A. J.], and Division of Hematology-Oncology, Children's Hospital of Los Angeles, Los Angeles, California 90027 [W. M. R., W. E. L.]

The regulation of urokinase (u-PA) and tissue plasminogen activator (t-PA) in cultured normal and neoplastic urothelium was examined because plasminogen activators (PAs) are thought to be important in malignancy. Both activators were synthesized by normal urothelial cells grown in vitro under chemically defined conditions. The level of t-PA activity decreased when normal urothelial cells reached saturation density, but was stimulated more than 10-fold by the addition of epidermal growth factor (EGF) to the culture medium. Northern blot analysis showed that the regulation occurred at the transcriptional level. On the other hand u-PA activity was regulated to a lower degree by EGF and was not affected by cell density. Immunohistochemical examination of urothelial cells in histology specimens showed that t-PA was present only in the apical cells facing the lumen, suggesting that the expression of the activity might be a marker for end-stage differentiation in vivo. In contrast to normal cells, tumor cell lines made only u-PA under all conditions tested, and the levels of its expression were either unaffected or slightly decreased by EGF. Tumor cells and normal cells therefore showed substantial differences in protease regulation by EGF.

¹ This work was supported by NIH Grants CA40422 and HL23500 and by a grant from the Cancer Research Society, Redlands, CA.

Received 3/15/88. Revised 6/27/88. Accepted 7/ 6/88.

This article has been cited by other articles:

				F.-M. Deng, M. Ding, R. M. Lavker, and T.-T. Sun Urothelial function reconsidered: A role in urinary protein secretion PNAS, January 2, 2001; 98(1): 154 - 159. [Abstract] [Full Text] [PDF]