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A Novel Expression Profile of Cell Cycle and DNA Repair Proteins in Nonfunctioning Pituitary Adenomas

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Abstract

The molecular mechanisms underlying the formation of nonfunctioning pituitary adenomas (NFAs) are largely unknown. In this study, we aimed to understand the relationship between NFAs and functional pituitary adenomas and the possible role of proteins involved in cell cycle, senescence, and DNA damage control mechanisms in the etiology of NFA. We analyzed pATM-S1981, pRb-S608, Rb, pE2F1-S364, p16, E2F1, p73, cyclin D1, and CHEK2 protein expression (in a group of 20 patients with acromegaly, 18 patients with Cushing’s disease (CD), and 29 NFA patients) by immunohistochemistry and their relevant mRNA expression by qRT-PCR (in a group of 7 patients with acromegaly, 7 patients with CD, and 7 NFA patients). The clinical and histopathological results on the patients were statistically evaluated. pE2F1-S364 protein expression in the CD group was significantly lower than that in the NFA and acromegaly groups (p = 0.025, p = 0.034, respectively). However, the expression of the p16 protein was lower than in the NFA group than in the CD and acromegaly groups (p = 0.030, p = 0.033, respectively), and E2F1 protein expression was significantly higher in the NFA group than in the CD group (p = 0.025). p73 protein expression in patients with acromegaly was significantly higher (p = 0.031) than that in the CD group. CHEK2 mRNA expression in the CD group was significantly higher than that in the acromegaly group (p = 0.012). The selective and tumor-specific associations between E2F1, pE2F1-S364, CHEK2, and p73 mRNA and protein levels indicate their involvement in pituitary adenoma formation in NFA, CD, and acromegaly patients.

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Abbreviations

ACTH:

adrenocorticotropic hormone

CD

Cushing’s disease

CDK

cyclin-dependent kinases

FSH

follicle-stimulating hormone

GH

growth hormone

LH

luteinizing hormone

NFA

nonfunctioning pituitary adenomas

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Acknowledgments

We are deeply grateful to Dr. Shlomo Melmed and all of his laboratory members at Cedars-Sinai Medical Center for their support and valuable recommendations.

Funding

The study was supported by the Research Fund of the Istanbul University, Istanbul, Turkey (project # 2017-25404)

Author information

Authors and Affiliations

  1. Department of Medical Biology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Derya Metin-Armagan & Melek Ozturk

  2. Department of Pathology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Nil Comunoglu

  3. Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Bahçeşehir University, Istanbul, Turkey

    Gulay Bulut

  4. Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Cerrahpasa, Istanbul, Turkey

    Pinar Kadioglu

  5. Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Hiraku Kameda

  6. Department of Neurosurgery, Istanbul Bilim University, Istanbul, Turkey

    Nurperi Gazioglu

  7. Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University- Cerrahpasa, Istanbul, Turkey

    Necmettin Tanriover

Authors
  1. Derya Metin-Armagan
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  2. Nil Comunoglu
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  3. Gulay Bulut
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  5. Hiraku Kameda
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  6. Nurperi Gazioglu
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  7. Necmettin Tanriover
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  8. Melek Ozturk
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Corresponding author

Correspondence to Melek Ozturk.

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The authors declare that they have no conflict of interest.

Ethical Approval

This study was approved by the Clinical Research Ethics Committee of Cerrahpaşa Medical School, Istanbul University, with the number 06/04/2017-133989. Written informed consent was obtained at the beginning of the study from all the patients.

All procedures involving human participants were performed in accordance with the ethical standards of the institutional research committee and of the 1964 Helsinki Declaration and its later amendments or comparable ethical standards

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Metin-Armagan, D., Comunoglu, N., Bulut, G. et al. A Novel Expression Profile of Cell Cycle and DNA Repair Proteins in Nonfunctioning Pituitary Adenomas. Endocr Pathol 31, 2–13 (2020). https://doi.org/10.1007/s12022-019-09598-x

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  • DOI: https://doi.org/10.1007/s12022-019-09598-x

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