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Down modulation of fibronectin messenger RNA in metastasizing rat prostatic cancer cells revealed by differential
J A Schalken1, S B Ebeling, J T Isaacs
1Department of Urology, Radboud University Hospital, Nijmegen, The Netherlands.
Abstract:
To identify genes whose expression is down modulated in the process of metastasis, gene expression was analyzed in cell lines derived from Dunning R-3327 rat prostatic tumor sublines. A complementary DNA (cDNA) library from the anaplastic nonmetastasizing subline AT-1 was used for a differential hybridization analysis, using probes derived from mRNAs of the AT-1 and the metastasizing MAT-LyLu subline. In this way 14 cDNA clones were isolated representing 6 differentially expressed genes. The expression levels in a panel of tumor sublines measured with these cDNA clones were tested for correlation with the anaplastic non-metastasizing phenotype. One cDNA clone, designated pSE-1, whose expression was high in all tested sublines with that phenotype, appeared to represent the gene for fibronectin. To further investigate the down modulation of this gene, we studied its expression in AT-2 (anaplastic, nonmetastasizing tumor) and lines derived therefrom that exhibited a high metastatic potential after transfection with the v-Ha-ras oncogene. In the genetically manipulated metastasizing tumor sublines, fibronectin mRNA levels were approximately 4- to 8-fold lowered compared to the nonmetastasizing parental AT-2 line.
Insights
This study identified fibronectin as a gene downregulated during prostate cancer metastasis. Lowered fibronectin mRNA levels were observed in metastasizing tumor sublines compared to non-metastasizing ones.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate cancer metastasis involves complex genetic alterations.
- Identifying genes that regulate metastasis is crucial for therapeutic development.
Purpose of the Study:
- To identify genes downregulated during prostate cancer metastasis.
- To investigate the role of fibronectin in the metastatic process.
Main Methods:
- Differential hybridization analysis of complementary DNA (cDNA) libraries from rat prostatic tumor sublines.
- Quantitative analysis of gene expression using cDNA clones.
- Investigating fibronectin mRNA levels in genetically manipulated tumor sublines.
Main Results:
- Six differentially expressed genes were identified, with one clone (pSE-1) representing fibronectin.
- Fibronectin expression was high in non-metastasizing sublines and low in metastasizing sublines.
- Fibronectin mRNA levels were significantly reduced (4- to 8-fold) in metastasizing tumor sublines compared to the parental non-metastasizing line.
Conclusions:
- Fibronectin gene expression is downmodulated during prostate cancer metastasis.
- Reduced fibronectin may contribute to the metastatic phenotype in prostate cancer.
- Further research into fibronectin's role could offer new therapeutic targets.