Kalthoff H, Schmiegel W, Roeder C, Kasche D, Schmidt A, Lauer G, Thiele H G, Honold G, Pantel K, Riethmüller G
Abteilung Immunologie, Medizinische Klinik, Universität Hamburg, Germany.
Oncogene. 1993 Feb;8(2):289-98.
We have analysed the expression of p53 at the mRNA level, and extensively at the protein level by immunostaining, Western blotting, and ELISA measurements revealing a p53 increase in 8 out of 14 cell lines established from human pancreatic carcinomas. The mRNA levels closely paralleled the protein levels in most of the cell lines. Overexpression of p53 in tumor cells correlated with mutations in the p53 gene. Immunocytochemistry was also performed with tissue cryosections showing a nuclear p53 staining in 8 out of 12 exocrine, and 2 out of 2 endocrine tumors. In addition, nonmalignant peri-tumoral tissue specimens and cells derived from pancreatic juice of acute pancreatic patients were also positively stained. These findings may suggest functions of p53 in stress situations induced by acute inflammation or tissue regeneration. Genomic mutations in the tumor suppressor gene were associated with point mutations in either codon 12, 13 or 61 in the c-K-RAS oncogene in about two-thirds of cell lines. The frequent activations of a RAS oncogene in combination with mutations of a tumor suppressor gene are likely to contribute to the malignant phenotype of pancreatic adenocarcinomas.
我们分析了p53在mRNA水平的表达，并通过免疫染色、蛋白质印迹法和酶联免疫吸附测定法在蛋白质水平进行了广泛分析，结果显示，在从人胰腺癌建立的14个细胞系中，有8个细胞系的p53表达增加。在大多数细胞系中，mRNA水平与蛋白质水平密切平行。肿瘤细胞中p53的过表达与p53基因的突变相关。我们还对组织冷冻切片进行了免疫细胞化学分析，结果显示，在12个外分泌肿瘤中有8个、2个内分泌肿瘤中有2个出现细胞核p53染色。此外，急性胰腺炎患者胰腺周围的非恶性组织标本以及胰腺液来源的细胞也呈阳性染色。这些发现可能提示p53在急性炎症或组织再生诱导的应激情况下的功能。在大约三分之二的细胞系中，肿瘤抑制基因的基因组突变与c-K-RAS癌基因中密码子12、13或61的点突变相关。RAS癌基因的频繁激活与肿瘤抑制基因的突变相结合，可能导致胰腺腺癌的恶性表型。
