Downregulation of several fibulin genes in prostate cancer

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Abstract
BACKGROUND Fibulins, encoded by FBLN genes, are extracellular matrix proteins influencing cell adhesion and migration. Altered expression of fibulins is associated with progression of several cancer types, but has not been studied in prostate cancer. METHODS Expression of FBLN1 (major splice forms C and D), FBLN4, FBLN5, SPOCK1, and TENC was compared between 47 prostate cancer samples and 13 benign prostatic tissues by quantitative RT‐PCR. Fibulin‐1 and fibulin‐5 expression was studied by immunohistochemistry. Effects of androgens and the DNA methylation inhibitor 5‐aza‐2′‐deoxycytidine on fibulin expression were investigated in different prostate cancer cell lines. RESULTS Our recent microarray analysis suggested downregulation of three fibulins, FBLN1, FBLN4, and FBLN5, in prostate cancer, while two further ECM genes, SPOCK1 (testican) and TENC (tenascin C), appeared upregulated or unchanged. These observations were corroborated by quantitative RT‐PCR. Accordingly, FBLN1 and FBLN4 were weakly expressed in carcinoma lines compared to normal prostate epithelial cells (PrECs). Only FBLN4 was induced by 5‐aza‐2′‐deoxycytidine, but its promoter was unmethylated. Androgen did not affect expression of FBLN genes. The FBLN1C and FBLN1D splice forms were coordinately expressed. Fibulin‐1 protein was weakly detectable in benign PrECs, but tended to accumulate in cancer cells. Fibulin‐5 was predominantly located in the stroma with a strong gradient from the periurethral to the peripheral zone, and lost in cancers. CONCLUSIONS Three FBLN genes are significantly downregulated in prostate cancer, whereas SPOCK1 is often upregulated. FBLN5 downregulation fits its postulated anticancerous function, whereas FBLN1 and FBLN4 behave different than in certain other cancers. Prostate 67: 1770–1780, 2007.

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