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P-Glycoprotein Is Positively Correlated with p53 Protein Accumulation in Human Colorectal Cancers
Authors:Mikio Oka  Kiyoshi Kounoura  Fumihiko Narasaki  Akira Sakamoto  Minoru Fukuda  Isao Matsuo  Koki Ikeda  Junji Tsurutani  Nobuhiro Ikuno  Katsuhisa Omagari  Yohei Mizuta  Hiroshi Soda  Jean M. Gudas  Shigeru Kohno
Affiliation:Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852;Amgen Inc., Thousand Oaks, CA, USA
Abstract: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 Pabl80l. 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 Pahl80l. 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 Pabl80. 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 .
Keywords:P-glycoprotein    p53    Colon cancer    Multidrug resistance    MDR1 gene
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