Abnormal activation of the Akt signaling pathway in adenoid cystic carcinoma
Adenoid cystic carcinoma (ACC) is an intriguing lesion because it shows a slow growth in the beginning, but a late poor prognosis due to perineural invasion, metastasis and recurrence. This study aimed to investigate whether Akt signaling would be deregulated in adenoid cystic carcinoma and its consequence in the expression of associated proteins.
The expression of the Akt, p-Akt, NFκB, β-catenin, cyclin D1 and COX-2 was assessed by immunohistochemistry in 10 cases of ACC, 17 cases of pleomorphic adenoma (PA), and 7 cases of normal salivary gland (NSG).
p-Akt was overexpressed in ACC when compared to NSG. NFκB, β-catenin, and COX-2 were overexpressed in ACC and PA when compared to NSG. Most proteins were slightly higher expressed in ACC than in PA, but they never reached significance. p-Akt expression positively correlated with NFκB, β-catenin, cyclin D1 and COX-2 in ACC and PA, while this correlation trended to be negative in for these proteins (except for NFκB) in NSG using Person’s correlation analysis, but without reaching significance.
Our results indicate an abnormal activation of Akt signaling pathway, which can be an important regulator of tumor biology in ACC. Activated Akt correlated with the expression of NFκB, β-catenin and COX-2, which can potentially influence cell survival in ACC.
KeywordsAkt NFκB Salivary gland tumors Adenoid cystic carcinoma Pleomorphic adenoma
The author Andre Luis Ribeiro Ribeiro is grateful to CAPES Foundation, Ministry of Education of Brazil, for funding his PhD scholarship (Grant no. 0698130).
This research was not funded by any grant.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This study was approved by the ethics committee of the Institute of Health Sciences at the Federal University of Pará (protocol number: 0047.0.073.000-11) and all procedures performed were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
For this type of study, formal consent is not required.
- 1.El-Nagar AK, Chan JKC, Grandis JR et al (2017) WHO classification of head and neck tumours, 4th edn. IARC Press, LyonGoogle Scholar
- 10.Dodd RL, Slevin NJ (2006) Salivary gland adenoid cystic carcinoma: a review of chemotherapy and molecular therapies. Oral Oncol 42:759–769. https://doi.org/10.1016/j.oraloncology.2006.01.001 CrossRefPubMedGoogle Scholar
- 15.Younes MN, Park YW, Yazici YD et al (2006) Concomitant inhibition of epidermal growth factor and vascular endothelial growth factor receptor tyrosine kinases reduces growth and metastasis of human salivary adenoid cystic carcinoma in an orthotopic nude mouse model. Mol Cancer Ther 5:2696–2705. https://doi.org/10.1158/1535-7163.MCT-05-0228 CrossRefPubMedGoogle Scholar
- 27.Scrima M, de Marco C, Fabiani F et al (2012) Signaling networks associated with AKT activation in non-small cell lung cancer (NSCLC): new insights on the role of phosphatydil-inositol-3 kinase. PLoS One 7(2):e30427. https://doi.org/10.1371/journal.pone.0030427 CrossRefPubMedPubMedCentralGoogle Scholar
- 41.Zhang G, Zhou X, Xue L et al (2005) Accumulation of cytoplasmic beta-catenin correlates with reduced expression of E-cadherin, but not with phosphorylated Akt in esophageal squamous cell carcinoma: immunohistochemical study. Pathol Int 55:310–317. https://doi.org/10.1111/j.1440-1827.2005.01840.x CrossRefPubMedGoogle Scholar