Goepfert T M, McCarthy M, Kittrell F S, Stephens C, Ullrich R L, Brinkley B R, Medina D
*Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
FASEB J. 2000 Nov;14(14):2221-9. doi: 10.1096/fj.00-0165com.
Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.
最近研究表明，p53基因缺失小鼠的乳腺上皮细胞发生肿瘤的风险增加。激素刺激显著增加了p53基因缺失的乳腺细胞的肿瘤发生率。在此我们证明，p53基因缺失的乳腺细胞产生的乳腺肿瘤高度非整倍体，超过70%的肿瘤细胞染色体数目改变，平均染色体数为56。p53基因缺失基因型且年龄小于14周的正常乳腺细胞在原代细胞培养中未表现出非整倍体现象。值得注意的是，激素黄体酮而非雌激素增加了形态正常的p53基因缺失乳腺上皮细胞的非整倍体发生率。此类细胞表现出40%的非整倍体率，平均染色体数为54。在p53基因缺失的肿瘤细胞或激素刺激的正常p53基因缺失细胞中检测到的非整倍体增加并未伴随中心体扩增。这些结果表明，在缺乏肿瘤抑制基因p53的情况下，正常水平的黄体酮可促进染色体不稳定。这些结果支持了基于人类流行病学和动物模型研究的新假说，即黄体酮显著增强乳腺肿瘤发生。
