Dysregulated Expression of Tensin 2 and Components of the PI3 Kinase/Akt Signaling Pathway in Human Thyroid Carcinoma

Erfani, Nasrollah; Fattahi, Mohammad Javad; Dabbaghmanesh, Mohammad Hossein; Mehrazmay, Mohammad; Monabati, Ahmad; Rasekhi Kazerouni, Akbar; Hafizi, Sassan; Ghaderi, Abbas

Dysregulated Expression of Tensin 2 and Components of the PI3 Kinase/Akt Signaling Pathway in Human Thyroid Carcinoma

Document Type : Original Article(s)

Authors

Nasrollah Erfani ¹

Mohammad Javad Fattahi ¹

Mohammad Hossein Dabbaghmanesh ²

Mohammad Mehrazmay ¹

Ahmad Monabati ³

Akbar Rasekhi Kazerouni ²

Sassan Hafizi ⁴

Abbas Ghaderi ¹^{, 5}

¹ Cancer Immunology Group, Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

² Endocrinology and Metabolism Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

³ Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

⁴ Institute of Biomedical and Biomolecular Science, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK

⁵ Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: The phosphatidylinositol 3-kinase/Akt signaling pathway is recognized as a key driver of cancer cell survival and proliferation, and is often contingent upon an impairment of expression/function of the PTEN tumor suppressor, a negative regulator of this pathway. In addition, the cytoskeletal signaling protein Tensin 2 has also been implicated as a negative regulator of this pathway. However, the PI3K pathway remains to be fully characterized in clinical thyroid carcinomas. The aim of this study is to determine the expression of components of the PI3K pathway in neoplastic and normal tissue sections obtained from patients with thyroid carcinoma.Methods: Tissues from 58 cases with thyroid carcinoma underwent immunohistochemistry for activated Akt (phosphorylated Akt, pAkt), Tensin 2 and PTEN.Results: A total of 100% of thyroid cancerous tissues were positive for pAkt staining compared to 67.9% of normal tissues. In contrast, 46.8% of cancer tissues were positive for Tensin 2 compared to 61.7% of normal tissues. For PTEN, 82.8% of cancerous tissues and 67.2% of normal tissues stained positive for this protein. There were no associations between the expression levels of the molecules with the patients’ clinicopathological characteristics.Conclusion:We have found evidence for an enhanced activation of the PI3K/Akt signaling pathway in clinical thyroid carcinoma tissues. This can be coupled with concomitant downregulation of Tensin 2. Further work is required to determine the relative significance of PTEN expression versus its activity in thyroid carcinoma in order to determine its role in the observed increased Akt activity.