Parafibromin expression is an independent prognostic factor for colorectal carcinomas

• Published in: Human pathology 2011-08, Vol.42 (8), p.1089-1102
• Main Authors: Zheng, Hua-chuan, MD, PhD, Wei, Zheng-li, MD, PhD, Xu, Xiao-yan, PhD, Nie, Xiao-cui, MD, Yang, Xue, MD, Takahashi, Hiroyuki, MD, PhD, Takano, Yasuo, MD, PhD
• Format: Article
• Language: English
• Subjects: Apoptosis; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cell cycle; Cell Line, Tumor; Cell Movement; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; DNA, Neoplasm - analysis; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression; Humans; Immunohistochemistry; In Situ Hybridization; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Metabolic disorders; Mutation; Neoplasm Invasiveness; Parafibromin; Pathogenesis; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Prognosis; Progression; Promoter Regions, Genetic - genetics; Protein Binding; Proteins; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; RNA, Messenger - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2010.10.024

Summary Parafibromin is a protein encoded by hyperparathyroidism 2 , and its down-regulated expression is involved in the pathogenesis of parathyroid, breast, and gastric carcinomas. This study aimed to clarify the roles of parafibromin expression in tumorigenesis, progression, and prognosis of colorectal carcinomas. Parafibromin-expressing plasmid was transfected into DLD-1 cells with the phenotypes, and related molecules were examined. Parafibromin expression was examined in colorectal samples by immunohistochemistry, in situ hybridization, Western blot, or reverse transcription polymerase chain reaction. It was found that parafibromin overexpression could cause G1 arrest and enhance differentiation of DLD-1 cells. There was a high expression of p21, p27, and cyclin E, but low expression of cyclin D1 messenger RNA, phospho-cdc2, and phospho-cdc25c proteins. Parafibromin could inhibit c-myc messenger RNA expression by binding to c-myc promoter. Expression levels of nuclear parafibromin and parafibromin messenger RNA were decreased from colorectal nonneoplastic mucosa and adenomas to carcinomas ( P < .05). Immunohistochemically, parafibromin expression was inversely correlated with tumor size, depth of invasion, lymph node metastasis, clinicopathologic staging, and poor prognosis of carcinomas ( P < .05). It was suggested that parafibromin overexpression might suppress cell cycle progression and promote differentiation of DLD-1 cells. Aberrant parafibromin expression possibly contributes to the pathogenesis, growth, invasion, and metastasis of colorectal carcinomas and could be regarded as an independent factor to indicate a favorable prognosis for patients with colorectal carcinomas.