Galand P, Jacobovitz D, Alexandre K
Laboratory of Cytology and Experimental Cancerology, School of Medicine, Free University of Brussels, Belgium.
Int J Cancer. 1988 Jan 15;41(1):155-61. doi: 10.1002/ijc.2910410127.
An immunohistochemical study of c-Ha-ras expression was performed on preneoplastic and neoplastic stages of diethylnitrosamine (DENA)-induced hepatocarcinogenesis in rats, using an antibody raised against a peptide sequence of the Ha-ras p21 product. Moderate to high immunostaining intensity was observed in the following hepatocytic lesions: (1) hepatocellular carcinomas (14/14) and associated neoplastic nodules (8/8) and foci of phenotypic alterations (35/40) (after 13-20 months of treatment); (2) neoplastic nodules (6/6) and associated foci (42/50) (after 5-9 months); (3) foci (10/10) (after 2 months); and (4) small, slowly growing foci (26/40) found 9 months after treatment with DENA without prior partial hepatectomy, resulting in low number of nodules and no tumor even after 15 months. No c-Ha-ras p21 was detected immunohistochemically in normal nor in regenerating rat liver. Our results indicate that increased Ha-ras expression is an early and stable event in liver lesions associated with hepatocarcinogenesis. They also imply that increased Ha-ras expression is insufficient (if at all implicated) for inducing fully malignant hepatocyte transformation. It might be indicative of cell populations at an increased transformation risk.
利用针对Ha-ras p21产物肽序列产生的抗体，对二乙基亚硝胺（DENA）诱导的大鼠肝癌发生的癌前和肿瘤阶段进行了c-Ha-ras表达的免疫组织化学研究。在以下肝细胞病变中观察到中度至高免疫染色强度：（1）肝细胞癌（14/14）、相关肿瘤结节（8/8）和表型改变灶（35/40）（治疗13 - 20个月后）；（2）肿瘤结节（6/6）和相关病灶（42/50）（5 - 9个月后）；（3）病灶（10/10）（2个月后）；以及（4）在未事先进行部分肝切除的情况下，DENA处理9个月后发现的小的、生长缓慢的病灶（26/40），即使在15个月后结节数量也很少且无肿瘤。在正常大鼠肝脏和再生大鼠肝脏中均未通过免疫组织化学检测到c-Ha-ras p21。我们的结果表明，Ha-ras表达增加是与肝癌发生相关的肝脏病变中的早期和稳定事件。它们还暗示，Ha-ras表达增加（如果有牵连的话）不足以诱导完全恶性的肝细胞转化。它可能表明细胞群体的转化风险增加。
