Upregulation of URI/RMP gene expression in cervical cancer by high-throughput tissue microarray analysis

Int J Clin Exp Pathol. 2013;6(4):669-77. Epub 2013 Mar 15.

Abstract

URI, or RMP, is a RNA polymerase II subunit RPB5-associated protein known to play essential roles in ubiquitination and transcription. Recently, we and others have shown that URI/RMP is also important for progression of hepatocellular carcinoma, ovarian, and prostate cancers. To identify the mechanistic basis of URI/RMP during multiple cellular processes, we investigated URI/RMP expression in a tissue microarray (TMA) containing multiple normal human tissues. The results showed that URI/RMP is ubiquitously but differentially expressed in these human tissues which partially explains its multiple cellular functions. To elucidate the role of URI/RMP during oncogenesis of multiple malignancies, especially the tumors of reproductive system, we analyzed URI/RMP expression in a TMA containing multiple reproductive system tumors. We did not observe significant difference of URI/RMP expression between cancerous and adjacent tissues of the prostate, breast, ovarian, and endometrial cancers. However, increased URI/RMP expression was observed in two of the three cases of cervical SCC (squamous cell carcinoma) cells compared to their adjacent epithelial cells. Moreover, we detected significantly upregulated URI/RMP expression not only in cervical cancers but also in pre-cancerous CINs (cervical intra-epithelial neoplasias) in a TMA that covers the whole spectrum of normal cervix, CINs, and cervical cancers. No difference of URI/RMP expression was observed between CINs and cervical cancers. Given the high risk of CINs (especially CIN3) turning into cervical cancer if left untreated, the increased URI/RMP expression in CINs as well as in cervical cancers suggest a clinical relevance of URI/RMP upon cervical cancer tumorigenesis and worth further investigation.

Keywords: URI/RMP; cervical cancer; immunohistochemistry; tissue microarray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Transformation, Neoplastic
  • Cervix Uteri / metabolism
  • Cervix Uteri / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • High-Throughput Screening Assays
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Repressor Proteins
  • Tissue Array Analysis*
  • Up-Regulation / physiology*
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • Repressor Proteins
  • URI1 protein, human