Galipeau P C, Cowan D S, Sanchez C A, Barrett M T, Emond M J, Levine D S, Rabinovitch P S, Reid B J
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7081-4. doi: 10.1073/pnas.93.14.7081.
Increased 4N (G2/tetraploid) cell populations have been postulated to be genetically unstable intermediates in the progression to many cancers, but the mechanism by which they develop and their relationship to instability have been difficult to investigate in humans in vivo. Barrett's esophagus is an excellent model system in which to investigate the order in which genetic and cell cycle abnormalities develop relative to each other during human neoplastic progression. Neoplastic progression in Barrett's esophagus is characterized by inactivation of the p53 gene, the development of increased 4N (G2/tetraploid) cell fractions, and the appearance of aneuploid cell populations. We investigated the hypothesis that patients whose biopsies have increased 4N (G2/tetraploid) cell fractions are predisposed to progression to aneuploidy and determined the relationship between inactivation of p53 and the development of 4N abnormalities in Barrett's epithelium. Our results indicate that increased 4N (G2/tetraploid) populations predict progression to aneuploidy and that the development of 4N abnormalities is interdependent with inactivation of the p53 gene in Barrett's esophagus in vivo.
增加的4N（G2/四倍体）细胞群体被认为是许多癌症进展过程中基因不稳定的中间体，但它们的产生机制及其与不稳定性的关系在人体体内很难进行研究。巴雷特食管是一个很好的模型系统，可用于研究在人类肿瘤进展过程中基因和细胞周期异常相对于彼此出现的顺序。巴雷特食管的肿瘤进展特征为p53基因失活、4N（G2/四倍体）细胞比例增加以及非整倍体细胞群体的出现。我们研究了活检中4N（G2/四倍体）细胞比例增加的患者易发展为非整倍体这一假说，并确定了p53失活与巴雷特上皮中4N异常发展之间的关系。我们的结果表明，增加的4N（G2/四倍体）群体预示着向非整倍体的进展，并且在体内巴雷特食管中，4N异常的发展与p53基因失活相互依存。
