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APOBEC3B high expression status is associated with aggressive phenotype in Japanese breast cancers

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Abstract

Background

The members of AID/APOBEC protein family possess cytidine deaminase activity that converts cytidine residue to uridine on DNA and RNA. Recent studies have shown the possible influence of APOBEC3B (A3B) as DNA mutators of breast cancer genome. However, the clinical significance of A3B expression in Japanese breast cancer has not been studied in detail.

Methods

Ninety-three primary breast cancer tissues (74 estrogen-receptor (ER) positive, 3 ER and HER2 positive, 6 HER2 positive, and 10 triple negative) including 37 tumor-normal pairs were assessed for A3B mRNA expression using quantitative real-time RT-PCR. We analyzed the relation between A3B expression, mutation analysis of TP53 and PIK3CA by direct sequencing, polymorphic A3B deletion allele and human papillomavirus (HPV) infection in tumors.

Results

A3B mRNA was overexpressed in tumors compared with normal tissue. Patients with high A3B expression were associated with subtype and progression of lymph node metastasis and pathological nuclear grade. However, the expression was not related to any other clinicopathological factors, including mutation of TP53 and PIK3CA, polymorphic A3B deletion allele, HPV infection and survival time.

Conclusion

The expression of A3B in breast cancer was higher than in non-cancerous tissues and was related to the lymph node metastasis and nuclear grade, which are reliable aggressive phenotype markers in breast cancer. Evaluation of A3B expression in tumor may be a marker for breast cancer with malignant potential.

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Acknowledgments

We thank Dr. Andrei Turtoi and all members of Department of Molecular Pharmacology and Oncology and Thoracic Visceral Organ Surgery for their helpful discussions. We also thank patients who participated in this study, and Ikuko Horikoshi and Tadashi Handa for their technical assistance. The work was supported in part by Uehara Zaidan, Promotion Plan for the Platform of Human Resource Development for Cancer and New Paradigms—Establishing Centers for Fostering Medical Researchers of the Future programs by Ministry of Education, Culture, Sports, Science and Technology of Japan, and Gunma University Initiative for Advanced Research (GIAR).

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Authors and Affiliations

  1. Department of Thoracic Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Miki Tsuboi, Jun Horiguchi, Hideaki Tokiniwa & Izumi Takeyoshi

  2. Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Miki Tsuboi, Arito Yamane, Takehiko Yokobori, Susumu Rokudai & Masahiko Nishiyama

  3. Initiative for Advanced Research, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Reika Kawabata-Iwakawa & Shinji Yoshiyama

  4. Diagnostic Pathology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Tetsunari Oyama

  5. Department of Surgery, Toho Hospital, 1155 Azami, Kasakake-machi, Midorishi, Gunma, 379-2311, Japan

    Hiroki Odawara

Authors
  1. Miki Tsuboi
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  2. Arito Yamane
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  10. Tetsunari Oyama
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  11. Izumi Takeyoshi
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  12. Masahiko Nishiyama
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Corresponding author

Correspondence to Masahiko Nishiyama.

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Conflict of interest

Masahiko Nishiyama received a research grant from Yakult Honsha Co. Ltd. The other authors declare that they have no conflict of interest.

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Tsuboi, M., Yamane, A., Horiguchi, J. et al. APOBEC3B high expression status is associated with aggressive phenotype in Japanese breast cancers. Breast Cancer 23, 780–788 (2016). https://doi.org/10.1007/s12282-015-0641-8

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  • DOI: https://doi.org/10.1007/s12282-015-0641-8

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