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 epidermal growth factor (EGF) was investigated in a human prostate cancer cell line.


METHODS
Secreted protein and messenger RNA were detected using Western and Northern methods, respectively. EGF receptor antibodies were used for neutralization of the EGF receptor to determine the role of the EGF growth factor family (EGF, transforming growth factor alpha (TGFalpha), or amphiregulin) in the basal induction of matrilysin.


RESULTS
EGF increased mRNA and secreted protein levels for the MMP matrilysin in LNCaP cells, in a concentration- and time-dependent manner. Transforming growth factor beta1 (TGFbeta1) had no inhibitory effect on the levels of mRNA or secreted protein induced by EGF in LNCaP cells. Decay of matrilysin mRNA after the addition of actinomycin D indicated that the half-life 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 matrilysin.


CONCLUSIONS
Exogenously added EGF increased matrilysin mRNA, perhaps at a transcriptional level. Growth factors, other than the members of the EGF family 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 LNCaP cells suggest that paracrine regulation of matrilysin expression in human prostate carcinoma cells could be via the EGF receptor.
Department of Radiation Oncology, Arizona Cancer Center, Tucson, Arizona 85724, USA.
P
P
Sundareshan
R B
RB
Nagle
G T
GT
Bowden
D000230:Adenocarcinoma; D003609:Dactinomycin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000235:genetics*; D011471:Prostatic Neoplasms; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7