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Parafibromin expression is an independent prognostic factor for colorectal carcinomas
- Source :
- Human pathology. 42(8)
- Publication Year :
- 2010
-
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.
- Subjects :
- Cyclin E
Parafibromin
Gene Expression
Apoptosis
Biology
medicine.disease_cause
Pathology and Forensic Medicine
Metastasis
Proto-Oncogene Proteins c-myc
Cyclin D1
Cell Movement
Cell Line, Tumor
Gene expression
medicine
Biomarkers, Tumor
Humans
Neoplasm Invasiveness
RNA, Messenger
Promoter Regions, Genetic
In Situ Hybridization
Tumor Suppressor Proteins
DNA, Neoplasm
medicine.disease
Prognosis
Immunohistochemistry
Reverse transcription polymerase chain reaction
Cancer research
Carcinogenesis
Colorectal Neoplasms
Protein Binding
Subjects
Details
- ISSN :
- 15328392
- Volume :
- 42
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Human pathology
- Accession number :
- edsair.doi.dedup.....52e2204ec93bc1ef7eee4a359aa16b81