FORMATION OF THE TETRAPLOID INTERMEDIATE IS ASSOCIATED WITH THE DEVELOPMENT OF CELLS WITH MORE THAN 4 CENTRIOLES IN THE ELASTASE SIMIAN VIRUS-40 TUMOR-ANTIGEN TRANSGENIC MOUSE MODEL OF PANCREATIC-CANCER
FORMATION OF THE TETRAPLOID INTERMEDIATE IS ASSOCIATED WITH THE DEVELOPMENT OF CELLS WITH MORE THAN 4 CENTRIOLES IN THE ELASTASE SIMIAN VIRUS-40 TUMOR-ANTIGEN TRANSGENIC MOUSE MODEL OF PANCREATIC-CANCER
复制标题
DOI：
10.1073/pnas.88.15.6427
复制
发表时间：
1991-08-01
影响因子：
11.1
通讯作者：
REID, BJ
中科院分区：
文献类型：
--
作者：
LEVINE, DS;SANCHEZ, CA;REID, BJ
在表达猴病毒40肿瘤抗原的转基因小鼠中，在弹性蛋白酶I基因的控制区下，胰腺癌的发展以四倍体和多个非整倍体细胞群的顺序出现为特征。这些转基因小鼠的胰腺组织在8至32天大时进行了研究。到18天时，几乎100%的腺泡细胞核具有免疫组织化学可检测到的肿瘤抗原。20天后，细胞DNA含量检测显示为四倍体细胞，并与间期细胞的出现有关，在电子显微镜下，胰腺组织的单个薄片中每细胞有5-11个中心粒。有丝分裂细胞也被观察到，每个细胞有5个或更多的中心粒并入两极或至少三极纺锤体的两极。这些观察表明，在弹性酶猴病毒40肿瘤抗原转基因小鼠胰腺肿瘤形成的二倍体-->；四倍体-->；非整倍体序列中，四倍体中间体的形成伴随着具有5个或更多中心粒的细胞的发育，这些细胞可以并入异常有丝分裂纺锤体的极点。我们推测，具有4个以上中心粒的细胞易于形成多极有丝分裂，从而可能产生具有染色体得失的子细胞，从而导致随后的非整倍体肿瘤的发展。
The development of pancreatic cancer in transgenic mice expressing the simian virus 40 tumor antigen placed under controlling regions of the elastase I gene is characterized by the sequential appearance of tetraploid and then multiple aneuploid cell populations. Pancreatic tissues from such transgenic mice were studied between 8 and 32 days of age. Virtually 100% of acinar cell nuclei had immunohistochemically detectable tumor antigen by 18 days. Tetraploid cells were demonstrated by DNA content now cytometry by 20 days and were associated with the appearance of interphase cells that had 5-11 centrioles per cell in single thin sections of pancreatic tissue examined by electron microscopy. Mitotic cells also were observed that had 5 or more centrioles per cell that were incorporated into the poles of bipolar or at least tripolar spindle apparatuses. These observations indicate that formation of the tetraploid intermediate in the diploid --> tetraploid --> aneuploid sequence of pancreatic tumor formation in elastase-simian virus 40 tumor antigen transgenic mice is accompanied by the development of cells with 5 or more centrioles that can be incorporated into the poles of abnormal mitotic spindles. We speculate that cells with more than 4 centrioles are predisposed to the formation of multipolar mitoses that may yield daughter cells with chromosomal gains and losses, resulting in the subsequent development of aneuploid tumors.