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.
Vijayakumar
Sapna
S
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
Garcia
Dawn
D
Hensel
Chuck H
CH
Banerjee
Mohua
M
Bracht
Todd
T
Xiang
Ruihua
R
Kagan
Jacob
J
Naylor
Susan L
SL
D000818:Animals; D045744:Cell Line, Tumor; D041322:Chromosomes, Human, Y / Q000235:genetics* / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D014183:Transplantation, Heterologous
D005819:Genetic Markers