Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control genes in normal and cancerous testicular tissue

Kevin M. Hopkins, Xiaojian Wang, Ana Berlin, Haiying Hang, Harshwardhan Thaker, Howard B. Lieberman

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Human and mouse paralogues of the evolutionarily conserved mammalian HRAD9 and Mrad9 cell cycle checkpoint control genes have been isolated and called HRAD9B and Mrad9B, respectively. HRAD9B encodes a protein that is 414 amino acids long and is 55% similar and 35% identical to the HRAD9 gene product. The Mrad9B protein is 398 amino acids long and is 50% similar and 35% identical to its paralogue. We demonstrate that the encoded human protein is nuclear and can physically interact with checkpoint proteins HRAD1, HRAD9, HHUS1, and HHUS1B, much like HRAD9. Northern blot analysis to detect tissue specificity indicates that the human and mouse genes are expressed pre-dominantly in the testis. The abundance of HRAD9B RNA, as judged by quantitative reverse transcription-PCR, is very low in most testicular tumors, particularly those of germ cell origin, i.e., seminomas, relative to normal testis control, nonseminomas, or Leydig tumor cells. RNA levels corresponding to HRAD17, another checkpoint control gene, demonstrated a similar pattern, but in general, higher quantities of this message were detected in samples. Furthermore, normal/tumor tissue differences were not as dramatic or consistent from sample to sample, especially for the seminomas. Our results demonstrate for the first time that HRAD9 and Mrad9 are part of a gene family and reveal a new genetic element encoding a product that interacts with multiple, known cell cycle check-point control proteins. The findings also indicate that HRAD9B can serve as a biomarker in particular for testicular seminomas and might be causally related to the disease.

Original languageEnglish (US)
Pages (from-to)5291-5298
Number of pages8
JournalCancer Research
Volume63
Issue number17
StatePublished - Sep 1 2003
Externally publishedYes

Fingerprint

Seminoma
Genes
Testis
Proteins
RNA
Leydig Cell Tumor
Amino Acids
cdc Genes
Organ Specificity
Testicular Neoplasms
Nuclear Proteins
Cell Cycle Checkpoints
Germ Cells
Northern Blotting
Reverse Transcription
Cell Cycle
Biomarkers
Polymerase Chain Reaction
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hopkins, K. M., Wang, X., Berlin, A., Hang, H., Thaker, H., & Lieberman, H. B. (2003). Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control genes in normal and cancerous testicular tissue. Cancer Research, 63(17), 5291-5298.

Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control genes in normal and cancerous testicular tissue. / Hopkins, Kevin M.; Wang, Xiaojian; Berlin, Ana; Hang, Haiying; Thaker, Harshwardhan; Lieberman, Howard B.

In: Cancer Research, Vol. 63, No. 17, 01.09.2003, p. 5291-5298.

Research output: Contribution to journalArticle

Hopkins, KM, Wang, X, Berlin, A, Hang, H, Thaker, H & Lieberman, HB 2003, 'Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control genes in normal and cancerous testicular tissue', Cancer Research, vol. 63, no. 17, pp. 5291-5298.
Hopkins, Kevin M. ; Wang, Xiaojian ; Berlin, Ana ; Hang, Haiying ; Thaker, Harshwardhan ; Lieberman, Howard B. / Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control genes in normal and cancerous testicular tissue. In: Cancer Research. 2003 ; Vol. 63, No. 17. pp. 5291-5298.
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