Lack of p53 and ras mutations in Helicobacter hepaticus-induced liver tumors in A/JCr mice.
Lack of p53 and ras mutations in Helicobacter hepaticus-induced liver tumors in A/JCr mice.
复制标题
A/JCr 小鼠肝螺杆菌诱导的肝脏肿瘤中缺乏 p53 和 ras 突变。
作者：
M. Sipowicz;C. Weghorst;Y. Shiao;G. Buzard;R. Calvert;M. Anver;L. Anderson;J. Rice
肝螺杆菌是一种新近发现的侵入小鼠肝脏的细菌，可引起慢性活动性肝炎，并可导致癌前病变、肝细胞腺瘤和癌的发生。这为研究慢性细菌感染引起的癌症发展机制建立了一个独特的动物模型。细菌相关肿瘤发生的一个可能机制是癌基因或肿瘤抑制基因的突变。由于ras癌基因突变在各种化学诱导和自发的小鼠肝癌中被广泛检测到，而p53抑癌基因的特定突变与人类慢性血吸虫感染所致的膀胱癌有关，我们研究了10只自然感染的A/JCR小鼠的25个肝癌组织中存在点突变的情况。20个腺瘤和5个癌的大小从0.1到2.3厘米不等，发生在肝脏，其病理特征广泛，包括肝炎、炎症、增生、肥大、白细胞浸润、坏死和局灶性表型改变。从福尔马林固定的石蜡包埋组织中提取的DNA样本经PCR/SSCP分析，分析的基因没有突变。在25个小鼠肝脏肿瘤中完全没有ras基因突变是不寻常的。其他基因可能是靶点，或者肝吸虫感染通过其他途径导致肝癌，而不是直接破坏DNA。
Helicobacter hepaticus is a recently discovered bacterium that invades mouse liver causing chronic active hepatitis followed by development of preneoplastic hepatocellular foci, hepatocellular adenomas and carcinomas. This establishes a unique animal model for study of the mechanisms of cancer development due to a chronic bacterial infection. A possible mechanism of bacteria-associated tumorigenesis is mutation of oncogenes or tumor suppressor genes. Since mutations in ras oncogenes have been widely detected in a variety of chemically induced and spontaneous mouse liver tumors and specific mutations in the p53 tumor suppressor gene have been associated with human bladder cancers attributed to chronic schistosomal infection, we studied exons 1 and 2 of the N-, K- and H-ras genes and exons 5-8 of the p53 gene for the presence of point mutations in 25 liver tumors from 10 naturally infected A/JCr mice, ranging in age from 16 to 24 months. The 20 adenomas and five carcinomas varied in size from 0.1 to 2.3 cm and arose in livers characterized by a wide assortment of pathological profiles, including hepatitis, inflammation, hyperplasia, hypertrophy, leukocyte infiltration, necrosis and focal phenotypic alteration. DNA samples extracted from formalin-fixed paraffin-embedded tissues were screened by PCR/SSCP analysis and showed no mutations in the analyzed genes. Complete absence of mutations in ras genes in 25 mouse liver tumors is unusual. Other genes may be targeted or H. hepaticus infection causes liver cancer through other pathways than direct damage to DNA.
DOI：
10.1073/pnas.83.16.5825
发表时间：
1986-08
影响因子：
11.1
作者：
R. Wiseman;S. Stowers;E. Miller;M. Anderson;J. Miller
通讯作者：
R. Wiseman;S. Stowers;E. Miller;M. Anderson;J. Miller
雄性 Fischer 344 大鼠缺乏胆碱饮食诱导的肝细胞癌中的 p53 突变。
影响因子：
4.7
作者：
Smith,ML;Yeleswarapu,L;Scalamogna,P;Locker,J;Lombardi,B
通讯作者：
Lombardi,B