Silverman J A, Kuhlmann E T, Zurlo J, Yager J D, Longnecker D S
Department of Pathology, Dartmouth Medical School, Hanover, New Hampshire 03756.
Mol Carcinog. 1990;3(6):379-86. doi: 10.1002/mc.2940030610.
We examined the pattern of expression of several proto-oncogenes during nonneoplastic growth and in acinar cell neoplasms in the rat pancreas. The levels of c-myc, c-raf-1, and c-Ki-ras mRNAs were increased in regenerating pancreata following surgical partial pancreatectomy and following administration of camostat. We also investigated proto-oncogene expression associated with the progression of pancreatic cancers in azaserine-treated rats. Injection of a single dose (30 mg/kg) of azaserine (O-diazoacetyl-L-serine) to 14-d-old rats leads to a variety of neoplastic lesions in the rat pancreas. Total RNA was isolated from lesions in various stages of tumor progression, including adenomas, carcinomas in situ, and invasive carcinomas. We observed increased expression of c-myc, c-raf-1, and c-Ki-ras in azaserine-induced adenomas and carcinomas. Actin expression was also increased in these tissues, whereas amylase expression was variable. However, when compared to the normal growing pancreas, the level of proto-oncogene expression in the adenomas and carcinomas was disproportionate to the degree of cellular division in those tissues. Thus, the alterations induced by azaserine apparently caused a deregulated increase in expression of cellular oncogenes associated with growth regulation.
我们研究了几种原癌基因在大鼠胰腺非肿瘤性生长及腺泡细胞瘤中的表达模式。在手术部分切除胰腺后以及给予卡莫司他后，再生胰腺中c-myc、c-raf-1和c-Ki-ras mRNA的水平升高。我们还研究了与氮杂丝氨酸处理的大鼠胰腺癌进展相关的原癌基因表达。给14日龄大鼠单次注射剂量为30mg/kg的氮杂丝氨酸（O-重氮乙酰基-L-丝氨酸）会导致大鼠胰腺出现多种肿瘤性病变。从肿瘤进展的各个阶段的病变中分离总RNA，这些病变包括腺瘤、原位癌和浸润性癌。我们观察到在氮杂丝氨酸诱导的腺瘤和癌中c-myc、c-raf-1和c-Ki-ras的表达增加。这些组织中肌动蛋白的表达也增加，而淀粉酶的表达则各不相同。然而，与正常生长的胰腺相比，腺瘤和癌中原癌基因的表达水平与这些组织中的细胞分裂程度不成比例。因此，氮杂丝氨酸诱导的改变显然导致了与生长调节相关的细胞癌基因表达的失控增加。
