PTX1 up-regulates interferon-β in prostate cancer cell line PC-3.

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PTX1 is a gene identified by subtractive hybridization on the basis that it is expressed in normal prostate and not in prostatic carcinoma. It is unrelated to the pituitary homeobox protein (Ptx1 or Pitx1) that regulates pituitary hormone gene expression, and its function is currently unknown. Recently, it was found to be identical to Erv41, an endoplasmic reticulum (ER) resident protein involved in protein trafficking between ER and Golgi. Our earlier study showed that ectopic expression of PTX1 in prostate cancer cell line, PC-3, induced cellular senescence. To study its mechanism of action, we transfected PC-3 cells with PTX1 expression construct and determined the genes that were up-regulated by PTX1 using gene expression profiling, reverse transcriptase-PCR, and promoter-luciferase reporter assay. Gene expression microarray analyses showed that interferon-β (IFN-β) and a number of IFN-inducible proteins, among other proteins, were up-regulated by PTX1 expression. Up-regulation of IFN-β by PTX1 was confirmed by RT-PCR and a PTX1 responsive element upstream from the IFN-β gene was identified by promoter-luciferase reporter assay. These results suggest that PTX1 may induce cellular senescence in PC-3 cells via the IFN-β pathway. However, ectopic expression of IFN-β in PC-3 cells did not induce senescence. Since PTX1-induced senescence in PC-3 cells cannot be explained by up-regulation of IFN-β alone, other PTX1-induced protein(s) may also be involved in this process.