We identified a novel gene named prostate cancer antigen (PCA)-1 that is highly expressed in prostate carcinoma. Knockdown analysis by using PCA-1 siRNAs revealed induction of apoptosis of prostate cancer cells and attenuation of tumor formation in nude mouse xenografts; these findings indicate that PCA-1 may serve as a target molecule for prostate cancer therapy. PCA-1 possesses a domain that is similar to the 2-oxoglutarate- and Fe(II)-dependent oxygenase domain of the E. coli AlkB protein. At present, 7 human proteins with this domain are identified and called the AlkB homolog (ABH) family. Our aim is to clarify whether the ABH family molecules are possible candidates as target molecules for an effective cancer therapy.
Immunohistochemical analysis of carcinoma specimens with the anti-ABH family molecule antibodies revealed that ABH4 and ABH8 were strongly expressed in breast cancer; ABH6, in colon cancer; and ABH5 and ABH8, in bladder cancer. Moreover, siRNAs against the ABH family molecules significantly suppressed the growth of cancer cells. We expect that the ABH family molecules may be novel molecular targets for cancer therapy.
