The human Y chromosome suppresses the tumorigenicity of PC-3, a human prostate cancer cell line, in athymic nude mice

The loss of the Y chromosome is a frequent numerical chromosomal abnormality observed in human prostate cancer. In cancer, loss of specific genetic material frequently accompanies simultaneous inactivation of tumor suppressor genes. It is not known whether the Y chromosome harbors such genes. To address the role of genes on the Y chromosome in human prostate cancer, we transferred a tagged Y chromosome into PC‐3, a human prostate cancer cell line lacking a Y chromosome. A human Y chromosome was tagged with the hisD gene and transferred to PC‐3 by microcell‐mediated chromosome transfer. Tumorigenicity of these PC‐3 hybrids was tested in vivo and in vitro, and the results were compared with those of the polymerase chain reaction analyses conducted on the PC‐3 hybrids using Y chromosome‐specific markers. Among 60 mice injected with 12 different PC‐3 hybrids (five mice per hybrid), tumor growth was apparent in only one mouse, whereas tumors grew in all mice injected with the parental PC‐3 cells. An in vitro assay showed that the Y chromosome did not suppress anchorage‐independent growth of PC‐3 cells. We found that addition of the Y chromosome suppressed tumor formation by PC‐3 in athymic nude mice, and that this block of tumorigenesis was independent of the in vitro growth properties of the cells. This observation suggests the presence of a gene important for prostate tumorigenesis on the Y chromosome. © 2005 Wiley‐Liss, Inc.