P‐Glycoprotein Is Positively Correlated with p53 Protein Accumulation in Human Colorectal Cancers

• Published in: Japanese Journal of Cancer Research Vol. 88; no. 8; pp. 738 - 742
• Main Authors: Oka, Mikio, Kounoura, Kiyoshi, Narasaki, Fumihiko, Sakamoto, Akira, Fukuda, Minoru, Matsuo, Isao, Ikeda, Koki, Tsurutani, Junji, Ikuno, Nobuhiro, Omagari, Katsuhisa, Mizuta, Yohei, Soda, Hiroshi, Gudas, Jean M., Kohno, Shigeru
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-1997; Japanese Cancer Association
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Antineoplastic agents; ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology; Biological and medical sciences; Colon cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Gene Expression Regulation, Neoplastic; General aspects; Genes, MDR; Genes, p53; Humans; MDR1 gene; Medical sciences; Multidrug resistance; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; p53; Pharmacology. Drug treatments; Promoter Regions, Genetic; P‐glycoprotein; Tumor Suppressor Protein p53 - biosynthesis; Adenocarcinoma; Antineoplastic agent; Human; Rectal disease; Gene product; P Glycoprotein; Malignant tumor; Gene expression; Colonic disease; TP53 Gene; Multiple resistance; Rectum; Digestive diseases; Intestinal disease; Colon; Mutation; Negative therapeutic reaction; Tumor suppressor gene
• ISSN: 0910-5050; 1349-7006; 1876-4673
• 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 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.