Expression of metalloproteinases in human prostate carcinoma and their role in invasion and metastasis.
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Author
Siadat-Pajouh, Majid.Issue Date
1991Advisor
Nagle, Raymond B.
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The University of Arizona.Rights
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.Abstract
Twenty five surgical specimens of malignant human prostate, 3 lymph nodes with metastatic prostate carcinoma, 5 benign prostate hyperplasia (BPH), 11 normal human prostates, as well as 3 human prostate cell lines (DU-145, PC3 and LNCaP) were examined for the expression of human matrix metalloproteinase-7 gene (MMP-7) from the human collagenase family (originally called PUMP-1 for putative metalloproteinase-1) (Majid Siadat-Pajouh et al. 1991). Northern blots were prepared using total RNA extracted from 18 prostate adenocarcinomas, 4 BPH, 2 lymph nodes with metastatic prostate carcinoma and 11 normal human prostates. When the northern blots were hybridized with ³²P labeled MMP-7 cDNA probes, a 1.2 Kb mRNA was detected in 14 out 18 prostate adenocarcinomas, 1 out of 4 BPH, 1 out of 2 metastatic lymph nodes, and 3 out of 11 normal prostates. The 3 human prostate cell lines did not show any evidence of MMP-7 transcript. In situ hybridization was conducted using a ³⁵S labeled MMP-7 cRNA. In situ hybridization was carried out on seven prostate adenocarcinomas, 2 BPH, and 3 metastatic lymph nodes. In situ hybridization revealed that the MMP-7 gene was expressed in the epithelial cells of primary prostate adenocarcinoma as well as invasive and metastatic cells. MMP-7 expression was also seen focally in some benign epithelial cells but not in inflammatory cells or stroma. The combined results of northern analysis and in situ hybridization indicated that 72% of prostate adenocarcinomas, 66% of metastatic prostatic lymph nodes, 40% of BPH and 27% of normal prostate tissues express MMP-7 transcripts. Additional northern blot analysis was performed using probes to human type IV collagenase, type I collagenase and Stromelysin I in human prostate adenocarcinoma as well as normal prostate tissues. The results indicated that 6 out of 10 adenocarcinoma samples and none of the 4 normal samples were positive for type IV collagenase transcripts. None of the tissues examined for the expression of type I collagenase and stromelysin I were found to express the transcripts of interest at detectable levels. A monclonal antibody was generated against a 10 mer synthetic peptide unique to MMP-7. This antibody was reactive with the native protein in frozen prostate tissues. These data suggest that certain metalloproteinases are differentially expressed in prostatic adenocarcinoma and may play a role in invasion and metastasis.Type
textDissertation-Reproduction (electronic)
Degree Name
Ph.D.Degree Level
doctoralDegree Program
Microbiology and ImmunologyGraduate College