title: Expression of NEDD4-1, a PTEN regulator, in gastric and colorectal carcinomas.
abstract: Recent studies have disclosed that NEDD4-1 regulates PTEN activity by ubiquitination. NEDD4-1 negatively regulates PTEN in cytosol and acts as an oncogenic protein. By contrast, NEDD4-1 promotes PTEN nuclear import and acts as a tumor suppressor. Despite the importance of NEDD4-1 in PTEN regulation in cancer cells, expression of NEDD4-1 protein in cancer tissues is unknown. The aim of this study was to analyze NEDD4-1 expression in colorectal and gastric cancer tissues. We investigated NEDD4-1 protein expression in 103 colorectal and 60 gastric carcinoma tissues by immunohistochemistry using a tissue microarray approach. In the cancers, expression of NEDD4-1 was detected in 82 (80%) of the colorectal carcinomas and 45 (75%) of the gastric carcinomas in cytoplasm. By contrast, the normal mucosal cells of both stomach and colon showed no or very weak expression of NEDD4-1. There was no significant association of NEDD4-1 expression with clinicopathologic characteristics, including invasion, metastasis and stage. Our data indicate that NEDD4-1 overexpression is a feature of both colorectal and gastric carcinomas. The increased expression of NEDD4-1 in malignant gastric and colorectal cells compared to their normal epithelial cells suggests that NEDD4-1 expression may play a role in colorectal and gastric cancer development.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Eun Goo
authors.initials: EG
authors.lastname: Jeong
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Kim
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D056827:Endosomal Sorting Complexes Required for Transport; D006801:Humans; D007150:Immunohistochemistry; D000075702:Nedd4 Ubiquitin Protein Ligases; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D040081:Protein Array Analysis / Q000379:methods; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; D044767:Ubiquitin-Protein Ligases; D051059:PTEN Phosphohydrolase