title: Parafibromin expression is an independent prognostic factor for colorectal carcinomas.
abstract: 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.
authors.affiliation: College of Basic Medicine, China Medical University, Shenyang 110001, China. zheng_huachuan@hotmail.com
authors.forename: Hua-chuan
authors.initials: HC
authors.lastname: Zheng
authors.forename: Zheng-li
authors.initials: ZL
authors.lastname: Wei
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Xu
authors.forename: Xiao-cui
authors.initials: XC
authors.lastname: Nie
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C454900:CDC73 protein, human; D004273:DNA, Neoplasm; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins