Oka M, Kounoura K, Narasaki F, Sakamoto A, Fukuda M, Matsuo I, Ikeda K, Tsurutani J, Ikuno N, Omagari K, Mizuta Y, Soda H, Gudas J M, Kohno S
Second Department of Internal Medicine, Nagasaki University School of Medicine.
Jpn J Cancer Res. 1997 Aug;88(8):738-42. doi: 10.1111/j.1349-7006.1997.tb00445.x.
To explore the relationship between mutant p53 and Pgp expression, we have examined the levels of both proteins in human colorectal adenocarcinomas. Serial frozen sections of 40 surgical samples were stained with an anti-Pgp (MRK16) and two different anti-p53 protein antibodies (Abs), PAb421 and PAb1801. Nineteen (47.5%) of 40 samples examined were positive for Pgp, and 18 (45%) of 40 were positive for p53. The samples that stained positively with PAb421 also stained positively with PAb1801. Pgp expression was detected in 13 (76.5%) of 17 samples that were positive for p53 using PAb421 and in 15 (83.3%) of 18 samples that were positive for p53 using PAb1801. Thus, we found that p53 and Pgp were co-expressed in a significant number of samples (P < 0.002). There was no relationship between Pgp or p53 protein accumulation and histologic grade or stage. The present results demonstrate that Pgp expression is closely associated with p53 protein accumulation in human colorectal cancers. These data provide evidence to support the idea that mutant p53 activates the MDR1 gene in vivo.
为了探究突变型p53与P-糖蛋白(Pgp)表达之间的关系,我们检测了人类结肠腺癌中这两种蛋白的水平。对40份手术样本的连续冰冻切片用抗Pgp(MRK16)以及两种不同的抗p53蛋白抗体(PAb421和PAb1801)进行染色。在检测的40份样本中,19份(47.5%)Pgp呈阳性,40份中有18份(45%)p53呈阳性。用PAb421染色呈阳性的样本用PAb1801染色也呈阳性。在使用PAb421检测p53呈阳性的17份样本中,13份(76.5%)检测到Pgp表达;在使用PAb1801检测p53呈阳性的18份样本中,15份(83.3%)检测到Pgp表达。因此,我们发现p53和Pgp在大量样本中共同表达(P < 0.002)。Pgp或p53蛋白积累与组织学分级或分期之间没有关系。目前的结果表明,在人类结直肠癌中,Pgp表达与p53蛋白积累密切相关。这些数据为支持突变型p53在体内激活多药耐药基因1(MDR1)这一观点提供了证据。