EGF induces the expression of matrilysin in the human prostate adenocarcinoma cell line, LNCaP

BACKGROUND. Matrix metalloproteinases (MMPs) are regulated both positively and negatively at the transcriptional level by a variety of growth factors, oncogenes, and tumor promoters. induction of the MMP, matrilysin, by epide rmal growth factor (EGF) was investigated in a human prostate cancer cell l ine. METHODS. Secreted protein and messenger RNA were detected using Western and Northern methods, respectively. EGF receptor antibodies were used for neut ralization of the EGF receptor to determine the role of the EGF growth fact or family (EGF, transforming growth factor alpha (TGF alpha), or amphiregul in) in the basal induction of matrilysin. RESULTS. EGF increased mRNA and secreted protein levels for the MMP matrily sin in LNCaP cells, in a concentration- and time-dependent manner. Transfor ming growth factor beta(1) (TGF beta(1)) had no inhibitory effect on the le vels of mRNA or secreted protein induced by EGF in LNCaP cells. Decay of ma trilysin mRNA after the addition of actinomycin D indicated that the half-l ife of matrilysin mRNA was not altered by EGF. Blocking with a neutralizing antibody to the EGF receptor did not alter the basal level of secreted mat rilysin. CONCLUSIONS. Exogenously added EGF increased matrilysin mRNA, perhaps at a transcriptional level. Growth factors, other than the members of the EGF fa mily which act through the EGF receptor, may be involved in the regulation of the basal level of secreted matrilysin in LNCaP cells. Our data with LNC aP cells suggest that paracrine regulation of matrilysin expression in huma n prostate carcinoma cells could be via the EGF receptor. (C) 1999 Wiley-Li ss, Inc.