Vijayakumar Sapna, Garcia Dawn, Hensel Chuck H, Banerjee Mohua, Bracht Todd, Xiang Ruihua, Kagan Jacob, Naylor Susan L
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
Genes Chromosomes Cancer. 2005 Dec;44(4):365-72. doi: 10.1002/gcc.20250.
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.
Y染色体缺失是在人类前列腺癌中观察到的常见染色体数目异常。在癌症中，特定遗传物质的缺失常常伴随着肿瘤抑制基因的同时失活。尚不清楚Y染色体是否含有此类基因。为了研究Y染色体上的基因在人类前列腺癌中的作用，我们将一条带有标记的Y染色体导入PC-3细胞，这是一种缺乏Y染色体的人类前列腺癌细胞系。用hisD基因标记一条人类Y染色体，并通过微细胞介导的染色体转移将其导入PC-3细胞。对这些PC-3杂交细胞的致瘤性进行了体内和体外测试，并将结果与使用Y染色体特异性标记对PC-3杂交细胞进行的聚合酶链反应分析结果进行了比较。在注射了12种不同PC-3杂交细胞的60只小鼠中（每种杂交细胞注射5只小鼠），只有1只小鼠出现肿瘤生长，而注射亲本PC-3细胞的所有小鼠都出现了肿瘤生长。体外试验表明，Y染色体并未抑制PC-3细胞的非锚定依赖性生长。我们发现，添加Y染色体可抑制无胸腺裸鼠中PC-3细胞的肿瘤形成，并且这种肿瘤发生的阻断与细胞的体外生长特性无关。这一观察结果表明Y染色体上存在一个对前列腺肿瘤发生很重要的基因。
