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Differential expression levels of β-catenin are associated with invasive behavior of both functional and non-functional pituitary neuroendocrine tumor (PitNET)

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Abstract

Background

Although research continues to elucidate the molecular mechanism underlying pituitary tumor pathogenesis, limited information is available on the potential role and expression profile of β-catenin in functional and non-functional pituitary neuroendocrine tumors (PitNETs).

Methods and results

In the current study, 104 pituitary samples (tumors and cadaveric healthy pituitary tissues) were included and the gene and protein expression levels of β-catenin were assessed by Real-Time PCR and immunohistochemistry, respectively. The correlation between expression level of β-catenin and tumor invasive feature and size as well as patient age, gender, and hormonal level was measured. The data showed that PitNET samples expressed higher levels of the β-catenin gene and protein compared to healthy pituitary tissues. Although there was no difference in β-catenin expression level between non-functioning (NF-PitNETs) and growth hormone-producing tumors (GH-PitNETs), both tumor types showed significantly elevated β-catenin levels compared to healthy pituitary tissues. The high level of β-catenin in the invasive functional and non-functional tumors is indicative of the association of β-catenin with PitNETs invasion. The expression pattern of the β-catenin gene and protein was consistently and significantly associated with these tumor types. The correlation between β-catenin and insulin-like growth factor 1 (IGF-1) in GH-PitNETs indicates the potential relevance of β-catenin and IGF-1 for GH-PitNETs.

Conclusions

The simultaneous increase in the expression of β-catenin gene and protein level in PitNET tissues and their relationship to the tumor severity indicates the possible contributing role of β-catenin and its underlying signaling mediators in PitNET pathogenesis.

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Abbreviations

GSK-3β:

Glycogen synthase kinase-3β

APC:

Adenomatous polyposis coli

TCF/Lef1:

T cell factor/lymphoid enhancer factor-1

NF-PitNETs:

Non-functioning pituitary tumors

GH- PitNETs:

Growth hormone producing pituitary tumors

ETSS:

Endoscopic transnasal transphenoidal surgery

LMO:

Legal Medicine Organization

GH:

Growth hormone

IGF-1:

Insulin-like growth factor 1

SEM:

Standard error mean

GSK:

Glycogen synthase kinase

EMT:

Epithelial-mesenchymal transition.

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Acknowledgements

We really appreciate all the patients who took part in this survey and provided us with their tissue samples. We also thank Dr. Mohammad E. Khamseh for his scientific assistance.

Funding

This work was financially supported by the Iran University of Medical Sciences (Grant Number: 94-04-30- 27725).

Author information

Authors and Affiliations

  1. Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, P.O. Box: 1449614535, Tehran, Iran

    S. Fahimeh Taghavi & Masoumeh Tavakoli-Yaraki

  2. Division of Vascular and Endovascular Neurosurgery, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran

    Mohammad Ghorbani

  3. Pathology Department, Firozgar Hospital, Iran University of Medical Sciences, Tehran, Iran

    Mahshid Panahi

  4. Department of Laboratory Medicine, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Shima Nazem

  5. Department of Immunology, School of medicine, Iran University of Medical Sciences, Tehran, Iran

    Milad Karimi

  6. Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Vahid Salimi

Authors
  1. S. Fahimeh Taghavi
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [S. Fahimeh Taghavi], [Mohammad Ghorbani], [Mahshid Panahi] ,[ Shima Nazem], [Milad Karimi], [Vahid Salimi]. The first draft of the manuscript was written by [Masoumeh Tavakoli-Yaraki] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Masoumeh Tavakoli-Yaraki.

Ethics declarations

Competing interests

No conflict of interest is declared by authors.

Ethics approval

The ethics committee of the Vice president of research of Iran University of Medical Sciences with ethics committee code: IR.IUMS.FMD.REC 1396.31841 approved this project ethically. All patients were informed about the project process and they consented to have their tumor tissue collected for the present study with written informed consent. The Legal Medicine Organization (LMO) provided healthy pituitary autopsies for the project with written and signed consent forms obtained from the first-degree relatives of deceased individuals [17]. This study was performed based on the guidelines of Helsinki Declaration.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent to publish

The authors affirm that human research participants provided informed consent for publication of the data in Table 1; Fig. 2.

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Taghavi, S.F., Ghorbani, M., Panahi, M. et al. Differential expression levels of β-catenin are associated with invasive behavior of both functional and non-functional pituitary neuroendocrine tumor (PitNET). Mol Biol Rep 50, 6425–6434 (2023). https://doi.org/10.1007/s11033-023-08523-0

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