Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4α in the pathogenesis of human cancer
| Autor: | Koichi Sumi, Patrick C. Reid, Shuying Jiang, Kabuto Takano, Toshiya Tanaka, Akira Watanabe, Mika Sugai, Makoto Naito, C Ikegame, Takao Hamakubo, Yutaka Midorikawa, Riuko Ohashi, Go Hasegawa, Y Hirayama, Yoshitaka Hippo, Hajime Umezu, Yasutoshi Uchiyama, Hiroyuki Aburatani, Juro Sakai, Kenji Daigo, Hiroko Iwanari, Tatsuhiko Kodama, Hiromitsu Hotta |
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| Rok vydání: | 2006 |
| Předmět: |
Male
endocrine system Pathology medicine.medical_specialty Lung Neoplasms Colorectal cancer Biology digestive system Pathology and Forensic Medicine Pathogenesis Antibody Specificity Stomach Neoplasms Neoplasms Biomarkers Tumor Tumor Cells Cultured medicine Animals Humans Tissue Distribution RNA Messenger RNA Neoplasm Promoter Regions Genetic Reverse Transcriptase Polymerase Chain Reaction Stomach Antibodies Monoclonal Intestinal metaplasia medicine.disease Small intestine Neoplasm Proteins Gene Expression Regulation Neoplastic Hepatocyte nuclear factors Cell Transformation Neoplastic medicine.anatomical_structure Hepatocyte Nuclear Factor 4 Immunohistochemistry Female Pancreas Precancerous Conditions |
| Zdroj: | The Journal of Pathology. 208:662-672 |
| ISSN: | 1096-9896 0022-3417 |
| DOI: | 10.1002/path.1928 |
| Popis: | Hepatocyte nuclear factor-4alpha (HNF4alpha) exists in multiple isoforms that are generated by alternative promoter (P1 and P2) usage and splicing. Here we establish monoclonal antibodies (mAbs) for detecting P1 and P2 promoter-driven HNF4alpha, and evaluate their expression in normal adult human tissues and surgically resected carcinomas of different origins. Using immunohistochemical analysis, we demonstrate that, while P1 promoter-driven HNF4alpha is expressed in hepatocytes, small intestine, colon, kidney and epididymis, P2 promoter-driven HNF4alpha is expressed in bile duct, pancreas, stomach, small intestine, colon and epididymis. Altered expression patterns of P1 and P2 promoter-driven HNF4alpha were observed in gastric, hepatocellular and colorectal carcinomas. HNF4alpha was expressed in lung metastases from renal cell, hepatocellular and colorectal carcinoma but was not observed in lung tumours. The P1 and P2 promoter-driven HNF4alpha expression pattern of tumour metastases correlated with the primary site of origin. P1 promoter-driven HNF4alpha was also found in intestinal metaplasia of the stomach. These data provide evidence for the tissue distribution of P1 and P2 promoter-driven HNF4alpha at the protein level and suggest that HNF4alpha may be a novel diagnostic marker for metastases of unknown primary. We propose that the dysregulation of alternative promoter usage of HNF4alpha is associated with the pathogenesis of certain cancers. |
| Databáze: | OpenAIRE |
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