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Breast Cancer Research and Treatment

, Volume 113, Issue 1, pp 43–58 | Cite as

Evidence for a role of the Simian Virus 40 in human breast carcinomas

  • M. Hachana
  • M. TrimecheEmail author
  • S. Ziadi
  • K. Amara
  • S. Korbi
Preclinical Study

Abstract

Aims of the study The aim of this study was to investigate whether the Simian Virus 40 (SV40) is implicated in human breast carcinomas (BC). Experimental design SV40 presence was investigated by PCR assays targeting the Tag, the regulatory, and the VP1 regions in 109 invasive breast ductal carcinomas from Tunisian women. We also examined the relationship between the presence of SV40 and promoter methylation status of 15 tumor-related genes. Immunohistochemistry was used to investigate the expression of Tag, estrogen and progesterone receptors, HER2, and P53. Results SV40 DNA sequences were detected in 22% of tumors and in only 1.8% of the matched non-tumoral tissues. Using immunohistochemistry, SV40 was detected in the tumor cells. Hypermethylation frequencies were 78% for RASSF1A, 66% for SHP1, 61% for HIN1 and BRCA1, 47% for P16 and ER, 42% for CDH1 and APC, 40% for BLU, 35% for DAPK, 34% for RARβ2, 27% for GSTP1, 17% for TIMP3, 14% for CCND2, and 8% for hMLH1. Interestingly, the frequencies of RASSF1A, SHP1, BRCA1, and TIMP3 methylation, and the mean of the methylation index (MI) were significantly higher in SV40-positive than in SV40-negative cases (P-values ranging from 0.043 to 0.003). Moreover, SV40 presence correlates with P53 protein accumulation (32.7% vs. 13.3%; P = 0.015) and HER2 low expression (3.7% vs. 28%; P = 0.008). We also found SV40 more frequently in patients over 50 years than in younger patients (34.8% vs. 12.3%; P = 0.006). Conclusions This study is the first to demonstrate the presence of SV40 in human BC and provides data supporting a role for this virus in the pathogenesis of these tumors.

Keywords

BRCA1 HER2 Human breast carcinomas Methylation P53 Simian Virus 40 TIMP3 Tumor suppressor genes Tunisia 

Notes

Acknowledgements

This work was supported by the « Ministère de l’Enseignement Supérieur, de la Recherche Scientifique et Technologie » and the « Ministère de la Santé Publique » of Tunisia. The authors thank Dr Regis A. Vilchez from the Baylor College of Medicine, Houston, TX, USA for his kind gift of the plasmids containing SV40 genomes and Professor P. Wikström from the Department of Medical Bioscience, Umea, Sweden for his kind gift paraffin-embedded tissue of a transgenic adenocarcinoma of the mouse prostate (TRAMP) positive for SV40 Tag expression. We also thank Intissar Toumi, Samir Jaafar, Chedia Haj Salah, and Houda Sghaer for their expert technical assistance.

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • M. Hachana
    • 1
  • M. Trimeche
    • 1
    Email author
  • S. Ziadi
    • 1
  • K. Amara
    • 1
  • S. Korbi
    • 1
  1. 1.Department of PathologyFarhat Hached HospitalSousseTunisia

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