PNA Medical Corner: Role of Proteins in Nonfunctioning Pituitary Adenomas

Nurperi Gazioglu2This month the PNA medical corner features an article co-written by PNA member Nurperi Gazioglu, a professor of neurosurgery at Istanbul University Cerrahpasa in Turkey. Researchers looked at the role cell cycle, senescence, and DNA damage control mechanisms play in the formation of nonfunctioning pituitary adenomas, acromegaly and Cushing’s Disease. They found that the impact varies by tumor type.

Endocr Pathol. 2019 Dec 11. doi: 10.1007/s12022-019-09598-x. [Epub ahead of print]
A Novel Expression Profile of Cell Cycle and DNA Repair Proteins in Nonfunctioning Pituitary Adenomas.
Metin-Armagan D1, Comunoglu N2, Bulut G3, Kadioglu P4, Kameda H5, Gazioglu N6, Tanriover N7, Ozturk M8.

Author information
1 Department of Medical Biology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey.
2 Department of Pathology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey.
3 Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Bahçeşehir University, Istanbul, Turkey.
4 Department of Endocrinology and Metabolism, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Cerrahpasa, Istanbul, Turkey.
5 Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
6 Department of Neurosurgery, Istanbul Bilim University, Istanbul, Turkey.
7 Department of Neurosurgery, Cerrahpasa Medical School, Istanbul University- Cerrahpasa, Istanbul, Turkey.
8 Department of Medical Biology, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Istanbul, Turkey. [email protected]

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.

KEYWORDS:
CHEK2; E2F1; Nonfunctioning pituitary adenomas; RB; p16; p73; pE2F1-S364
PMID:31828584 DOI: 10.1007/s12022-019-09598-x

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