Ukr.Biochem.J. 2016; Volume 88, Issue 5, Sep-Oct, pp. 90-95

doi: https://doi.org/10.15407/ubj88.05.090

Protein kinase Akt activity in human thyroid tumors

07.11.2016   Uncategorized   No comments

B. B. Guda, V. V. Pushkarev, O. V. Zhuravel, A. Ye. Kovalenko,
V. M. Pushkarev, Y. M. Taraschenko, M. D. Tronko

State Institution V. P. Komisarenko Institute of Endocrinology and Metabolism,
National Academy of Medical Sciences of Ukraine, Kyiv;
e-mail: pushkarev.vm@gmail.com

We studied the expression and activation of the main effector protein kinase of phosphatidylinositol-3-kinase cascade (PI3K) – Akt in conventionally normal tissues, benign and highly differentiated (with and without metastases) human thyroid tumors. There was a difference in the Akt1 amount in tumor tissue compared with normal tissue in papillary carcinomas and tissue of multinodular goiter. Akt expression both in tumor and conventionally normal tissues of follicular adenoma was significantly lower than in follicular carcinoma. The lowest level of Akt expression was observed in tissues of multinodular goiter. Total activity of all three isoforms of Akt1/2/3 was lower in tumors compared to conventionally normal tissue. Thus, Akt activity (according to Thr308 phosphorylation) is not associated with proliferative processes in the tumor tissue of the thyroid. Apoptosis level detected in these tissues was not associated with the protein kinase activity either. Possible mechanisms of signaling cascade PI3K/Akt inhibition in thyroid tumors are discussed.

Keywords: , ,

References:

  1. Liu Q, Turner KM, Alfred Yung WK, Chen K, Zhang W. Role of AKT signaling in DNA repair and clinical response to cancer therapy. Neuro Oncol. 2014 Oct;16(10):1313-23. PubMed, PubMedCentral, CrossRef
  2. Kumar A, Rajendran V, Sethumadhavan R, Purohit R. AKT kinase pathway: a leading target in cancer research. Sci World J. 2013 Nov 13;2013:756134. PubMed, PubMedCentral  CrossRef
  3. Xing M. Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer. Thyroid. 2010 Jul;20(7):697-706. PubMed, PubMedCentral CrossRef
  4. Pushkarov VV,  Kovzun OI, Popadiuk ID, Pushkarev VM, Tronko MD. The role of the signal cascade Ras/PI3K/Akt in the formation of the resistance of thyroid anaplastic cancer cells to paclitaxel. Rep Nat Acad Sci Ukraine. 2011;(3):169-171.
  5. Guda BB, Pushkarev VM, Pushkarev VV, Kovalenko AYe, Taraschenko YM, Kovzun OI, Tronko MD. The expression and activation of extracellular signal-regulated kinase-1/2 and proliferating cell nuclear antigen content in normal tissue and human thyroid tumors. SM J Endocrinol Metab. 2015;1(1):1002.
  6. Zhang X, Tang N, Hadden TJ, Rishi AK. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 2011 Nov;1813(11):1978-86. PubMed,  CrossRef
  7. Shimura T. Acquired radioresistance of cancer and the AKT/GSK3β/cyclin D1 overexpression cycle. J Radiat Res. 2011;52(5):539-44. PubMed,  CrossRef
  8. Wilks ST. Potential of overcoming resistance to HER2-targeted therapies through the PI3K/Akt/mTOR pathway. Breast. 2015 Oct;24(5):548-55. PubMed,   CrossRef
  9. Xu Y, Li N, Xiang R, Sun P. Emerging roles of the p38 MAPK and PI3K/AKT/mTOR pathways in oncogene-induced senescence. Trends Biochem Sci. 2014 Jun;39(6):268-76. PubMed, PubMedCentral CrossRef
  10. Sin S, Kim SY, Kim SS. Chronic treatment with ginsenoside Rg3 induces Akt-dependent senescence in human glioma cells. Int J Oncol. 2012 Nov;41(5):1669-74. PubMed, CrossRef
  11. Wang CY, Kim HH, Hiroi Y, Sawada N, Salomone S, Benjamin LE, Walsh K, Moskowitz MA, Liao JK. Obesity increases vascular senescence and susceptibility to ischemic injury through chronic activation of Akt and mTOR. Sci Signal. 2009 Mar 17;2(62):ra11.  PubMed, PubMedCentral, CrossRef
  12. Taylor JR, Lehmann BD, Chappell WH, Abrams SL, Steelman LS, McCubrey JA. Cooperative effects of Akt-1 and Raf-1 on the induction of cellular senescence in doxorubicin or tamoxifen treated breast cancer cells. Oncotarget. 2011 Aug;2(8):610-26. PubMed, PubMedCentral, CrossRef
  13. Ying Y, Zhu H, Liang Z, Ma X, Li S. GLP1 protects cardiomyocytes from palmitate-induced apoptosis via Akt/GSK3b/b-catenin pathway. J Mol Endocrinol. 2015 Dec;55(3):245-62. PubMed, PubMedCentral, CrossRef
  14. Toker A. Achieving specificity in Akt signaling in cancer. Adv Biol Regul. 2012 Jan;52(1):78-87. Review. PubMed, PubMedCentral, CrossRef
  15. Park JI, Strock CJ, Ball DW, Nelkin BD. The Ras/Raf/MEK/extracellular signal-regulated kinase pathway induces autocrine-paracrine growth inhibition via the leukemia inhibitory factor/JAK/STAT pathway. Mol Cell Biol. 2003 Jan;23(2):543-54. PubMed, PubMedCentral, CrossRef
  16. Mooi WJ, Peeper DS. Oncogene-induced cell senescence–halting on the road to cancer. N Engl J Med. 2006 Sep 7;355(10):1037-46. Review. PubMed, CrossRef
  17. Hong SK, Yoon S, Moelling C, Arthan D, Park JI. Noncatalytic function of ERK1/2 can promote Raf/MEK/ERK-mediated growth arrest signaling. J Biol Chem. 2009 Nov 27;284(48):33006-18. PubMed, PubMedCentral, CrossRef
  18. Park JI. Growth arrest signaling of the Raf/MEK/ERK pathway in cancer. Front Biol (Beijing). 2014 Feb;9(2):95-103. PubMed, PubMedCentral, CrossRef
  19. Wu PK, Hong SK, Veeranki S, Karkhanis M, Starenki D, Plaza JA, Park JI. A mortalin/HSPA9-mediated switch in tumor-suppressive signaling of Raf/MEK/extracellular signal-regulated kinase. Mol Cell Biol. 2013 Oct;33(20):4051-67. PubMed, PubMedCentral, CrossRef
  20. Bruhn MA, Pearson RB, Hannan RD, Sheppard KE. AKT-independent PI3-K signaling in cancer – emerging role for SGK3. Cancer Manag Res. 2013 Aug 26;5:281-92.  Review. PubMed, PubMedCentral, CrossRef
  21. Hemmings BA, Restuccia DF. PI3K-PKB/Akt pathway. Cold Spring Harb Perspect Biol. 2012 Sep 1;4(9):a011189.  PubMed, PubMedCentral, CrossRef
  22. Mahajan K, Mahajan NP. PI3K-independent AKT activation in cancers: a treasure trove for novel therapeutics. J Cell Physiol. 2012 Sep;227(9):3178-84. Review. PubMed, PubMedCentral, CrossRef
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