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BUB1 mRNA is significantly co-expressed with AURKA and AURKB mRNA in advanced-stage ovarian serous carcinoma

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Abstract

The objective of this study was to investigate the expression and clinical role of the spindle checkpoint kinase budding uninhibited by benzimidazole 1 (Bub1) in primary and metastatic advanced-stage ovarian serous carcinoma. BUB1 mRNA expression was analyzed in 178 tumors (88 effusions, 38 primary carcinomas, and 52 solid metastases) from 144 patients with advanced-stage disease using quantitative real-time polymerase chain reaction (PCR). Bub1 protein expression by Western blotting was studied in 63 carcinomas (30 effusions and 33 solid lesions). BUB1 mRNA expression at different anatomic sites was studied for association with clinicopathologic parameters, including chemotherapy resistance and survival. BUB1 mRNA was universally expressed in serous carcinomas, irrespective of anatomic site. BUB1 mRNA levels were uniformly low in six ovarian surface epithelium specimens analyzed for comparative purposes. Bub1 protein was expressed in 22/30 effusions and 28/33 solid lesions. BUB1 mRNA expression was significantly higher in chemo-naïve primary carcinomas and solid metastases compared to specimens obtained following neoadjuvant chemotherapy (p < 0.001) and was unrelated to chemotherapy exposure in effusions nor to chemoresponse or survival at any anatomic site. BUB1 mRNA levels in both effusions and solid lesions were strongly related to the mRNA levels of AURKA and AURKB previously studied in this cohort (p < 0.001 for both). Bub1 is widely expressed in primary and metastatic OC, suggesting a biological role in this cancer. BUB1 mRNA levels are lower following chemotherapy exposure in solid lesions, though its presence is unrelated to clinical behavior including response to chemotherapy and survival. BUB1 is co-expressed with AURKA and AURKB suggesting biological relationship between these spindle cell components.

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Acknowledgment

This work was supported by the Inger and John Fredriksen Foundation for Ovarian Cancer Research.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0424, Oslo, Norway

    Ben Davidson & Dag Andre Nymoen

  2. University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, N-0316, Oslo, Norway

    Ben Davidson, Anne Cathrine Staff & Claes G. Tropé

  3. Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0424, Oslo, Norway

    Bente Vilming Elgaaen & Thea E. Hetland Falkenthal

  4. Department of Obstetrics and Gynaecology, Oslo University Hospital, N-0424, Oslo, Norway

    Anne Cathrine Staff

  5. Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0424, Oslo, Norway

    Claes G. Tropé & Janne Kærn

  6. Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel

    Reuven Reich

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  1. Ben Davidson
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  2. Dag Andre Nymoen
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  3. Bente Vilming Elgaaen
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  4. Anne Cathrine Staff
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  5. Claes G. Tropé
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Corresponding author

Correspondence to Ben Davidson.

Additional information

Reuven Reich is affiliated with the David R. Bloom Center for Pharmacy and the Adolf and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics at The Hebrew University of Jerusalem, Israel.

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Davidson, B., Nymoen, D.A., Elgaaen, B.V. et al. BUB1 mRNA is significantly co-expressed with AURKA and AURKB mRNA in advanced-stage ovarian serous carcinoma. Virchows Arch 464, 701–707 (2014). https://doi.org/10.1007/s00428-014-1577-7

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  • DOI: https://doi.org/10.1007/s00428-014-1577-7

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