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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2012 | Research

Determination of SGK1 mRNA in non-small cell lung cancer samples underlines high expression in squamous cell carcinomas

Authors: Claudia Abbruzzese, Stefano Mattarocci, Laura Pizzuti, Anna M Mileo, Paolo Visca, Barbara Antoniani, Gabriele Alessandrini, Francesco Facciolo, Rosario Amato, Lucia D'Antona, Massimo Rinaldi, Armando Felsani, Nicola Perrotti, Marco G Paggi

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2012

Abstract

Background

Lung cancer represents the most frequent cause of death for cancer. In non-small cell lung cancer (NSCLC), which accounts for the vast majority of this disease, only early detection and treatment, when possible, may significantly affect patient's prognosis. An important role in NSCLC malignancy is attributed to the signal transduction pathways involving PI3Kinase, with consequent activation of the AKT family factors. The serum and glucocorticoid kinase (SGK) factors, which share high structural and functional homologies with the AKT factors, are a family of ubiquitously expressed serine/threonine kinases under the control of cellular stress and hormones. SGK1 is the most represented SGK member.

Methods

By means of immunohistochemistry and quantitative real-time PCR, we determined SGK1 protein and mRNA expression in a cohort of 66 formalin-fixed, paraffin-embedded NSCLC surgical samples. All samples belonged to patients with a well-documented clinical history.

Results

mRNA expression was significantly higher in squamous cell carcinomas, and correlated with several clinical prognostic indicators, being elevated in high-grade tumors and in tumors with bigger size and worse clinical stage. No correlation was found between SGK1 protein expression and these clinical parameters.

Conclusions

This explorative analysis of SGK1 expression in NSCLC samples highlights the potential role of this factor in NSCLC patients' prognosis. Moreover, the higher expression in the squamous cell carcinoma subtype opens new therapeutic possibilities in this NSCLC subtype by designing specific kinase inhibitors.

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Herbst RS, Heymach JV, Lippman SM: Lung cancer. N Engl J Med. 2008, 359: 1367-1380. 10.1056/NEJMra0802714.CrossRefPubMed

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 2009, 59: 225-249. 10.3322/caac.20006.CrossRefPubMed

Boffetta P: Epidemiology of environmental and occupational cancer. Oncogene. 2004, 23: 6392-6403. 10.1038/sj.onc.1207715.CrossRefPubMed

Patel JD: Lung cancer in women. J Clin Oncol. 2005, 23: 3212-3218. 10.1200/JCO.2005.11.486.CrossRefPubMed

Subramanian J, Govindan R: Lung cancer in never smokers: a review. J Clin Oncol. 2007, 25: 561-570. 10.1200/JCO.2006.06.8015.CrossRefPubMed

Samet JM, Avila-Tang E, Boffetta P, Hannan LM, Olivo-Marston S, Thun MJ: Lung cancer in never smokers: clinical epidemiology and environmental risk factors. Clin Cancer Res. 2009, 15: 5626-5645. 10.1158/1078-0432.CCR-09-0376.PubMedCentralCrossRefPubMed

Paggi MG, Vona R, Abbruzzese C, Malorni W: Gender-related disparities in non-small cell lung cancer. Cancer Lett. 2010, 298: 1-8. 10.1016/j.canlet.2010.08.009.CrossRefPubMed

Miller VA, Kris MG, Shah N, Patel J, Azzoli C, Gomez J: Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol. 2004, 22: 1103-1109. 10.1200/JCO.2004.08.158.CrossRefPubMed

Schlessinger J: Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell. 2002, 110: 669-672. 10.1016/S0092-8674(02)00966-2.CrossRefPubMed

10.

Pollak M: Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008, 8: 915-928. 10.1038/nrc2536.CrossRefPubMed

11.

Mattarocci S, Abbruzzese C, Mileo AM, Visca P, Antoniani B, Alessandrini G: Intracellular presence of insulin and its phosphorylated receptor in non-small cell lung cancer. J Cell Physiol. 2009, 221: 766-770. 10.1002/jcp.21916.CrossRefPubMed

12.

Bellacosa A, Kumar CC, Di Cristofano A, Testa JR: Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv Cancer Res. 2005, 94: 29-86.CrossRefPubMed

13.

Ruggero D, Sonenberg N: The Akt of translational control. Oncogene. 2005, 24: 7426-7434. 10.1038/sj.onc.1209098.CrossRefPubMed

14.

Testa JR, Tsichlis PN: AKT signaling in normal and malignant cells. Oncogene. 2005, 24: 7391-7393. 10.1038/sj.onc.1209100.CrossRefPubMed

15.

Bruhn MA, Pearson RB, Hannan RD, Sheppard KE: Second AKT: the rise of SGK in cancer signalling. Growth Factors. 2010, 28: 394-408. 10.3109/08977194.2010.518616.CrossRefPubMed

16.

Lang F, Bohmer C, Palmada M, Seebohm G, Strutz-Seebohm N, Vallon V: (Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms. Physiol Rev. 2006, 86: 1151-1178. 10.1152/physrev.00050.2005.CrossRefPubMed

17.

Liu D, Yang X, Songyang Z: Identification of CISK, a new member of the SGK kinase family that promotes IL-3-dependent survival. Curr Biol. 2000, 10: 1233-1236. 10.1016/S0960-9822(00)00733-8.CrossRefPubMed

18.

Mikosz CA, Brickley DR, Sharkey MS, Moran TW, Conzen SD: Glucocorticoid receptor-mediated protection from apoptosis is associated with induction of the serine/threonine survival kinase gene, sgk-1. J Biol Chem. 2001, 276: 16649-16654. 10.1074/jbc.M010842200.CrossRefPubMed

19.

Tangir J, Bonafe N, Gilmore-Hebert M, Henegariu O, Chambers SK: SGK1, a potential regulator of c-fms related breast cancer aggressiveness. Clin Exp Metastasis. 2004, 21: 477-483. 10.1007/s10585-004-4226-8.CrossRefPubMed

20.

Failor KL, Desyatnikov Y, Finger LA, Firestone GL: Glucocorticoid-induced degradation of glycogen synthase kinase-3 protein is triggered by serum- and glucocorticoid-induced protein kinase and Akt signaling and controls beta-catenin dynamics and tight junction formation in mammary epithelial tumor cells. Mol Endocrinol. 2007, 21: 2403-2415. 10.1210/me.2007-0143.CrossRefPubMed

21.

Cronin M, Pho M, Dutta D, Stephans JC, Shak S, Kiefer MC: Measurement of gene expression in archival paraffin-embedded tissues: development and performance of a 92-gene reverse transcriptase-polymerase chain reaction assay. Am J Pathol. 2004, 164: 35-42. 10.1016/S0002-9440(10)63093-3.PubMedCentralCrossRefPubMed

22.

Antonov J, Goldstein DR, Oberli A, Baltzer A, Pirotta M, Fleischmann A: Reliable gene expression measurements from degraded RNA by quantitative real-time PCR depend on short amplicons and a proper normalization. Lab Invest. 2005, 85: 1040-1050. 10.1038/labinvest.3700303.CrossRefPubMed

23.

Bianchi F, Nicassio F, Di Fiore PP: Unbiased vs. biased approaches to the identification of cancer signatures: the case of lung cancer. Cell Cycle. 2008, 7: 729-734. 10.4161/cc.7.6.5591.CrossRefPubMed

24.

Guan P, Huang D, He M, Zhou B: Lung cancer gene expression database analysis incorporating prior knowledge with support vector machine-based classification method. J Exp Clin Cancer Res. 2009, 28: 103-10.1186/1756-9966-28-103.PubMedCentralCrossRefPubMed

25.

Nakashima RA, Paggi MG, Pedersen PL: Contributions of glycolysis and oxydative phosphorylation to adenosine-5'-triphosphate production in AS-30D hepatoma cells. Cancer Res. 1984, 44: 5702-5706.PubMed

26.

Nakashima RA, Paggi MG, Arora KK, Pedersen PL: Integration of mitochondrial function with high aerobic glycolysis in tumors: role of hexokinase binding to the outer mitochondrial membrane. Integration of Mitochondrial Function. Edited by: Lemasters JJ, Hackenbrock CR, Thurman RG, Westhoff HV. 1990, New York, N.Y.: Plenum Publishing Company, 405-411.

27.

Wallace DC: Mitochondria and cancer: Warburg addressed. Cold Spring Harb Symp Quant Biol. 2005, 70: 363-374. 10.1101/sqb.2005.70.035.CrossRefPubMed

28.

Pedersen PL: Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers' most common phenotypes, the "Warburg Effect", i.e., elevated glycolysis in the presence of oxygen. J Bioenerg Biomembr. 2007, 39: 211-222. 10.1007/s10863-007-9094-x.CrossRefPubMed

29.

Brickley DR, Mikosz CA, Hagan CR, Conzen SD: Ubiquitin modification of serum and glucocorticoid-induced protein kinase-1 (SGK-1). J Biol Chem. 2002, 277: 43064-43070. 10.1074/jbc.M207604200.CrossRefPubMed

30.

Mattmann ME, Stoops SL, Lindsley CW: Inhibition of Akt with small molecules and biologics: historical perspective and current status of the patent landscape. Expert Opin Ther Pat. 2011, 21: 1309-1338. 10.1517/13543776.2011.587959.PubMedCentralCrossRefPubMed

31.

Morrow JK, Du-Cuny L, Chen L, Meuillet EJ, Mash EA, Powis G: Recent development of anticancer therapeutics targeting Akt. Recent Pat Anticancer Drug Discov. 2011, 6: 146-159. 10.2174/157489211793980079.PubMedCentralCrossRefPubMed

32.

Hixon ML, Paccagnella L, Millham R, Perez-Olle R, Gualberto A: Development of inhibitors of the IGF-IR/PI3K/Akt/mTOR pathway. Rev Recent Clin Trials. 2010, 5: 189-208. 10.2174/157488710792007329.CrossRefPubMed

Title: Determination of SGK1 mRNA in non-small cell lung cancer samples underlines high expression in squamous cell carcinomas
Authors: Claudia Abbruzzese
Stefano Mattarocci
Laura Pizzuti
Anna M Mileo
Paolo Visca
Barbara Antoniani
Gabriele Alessandrini
Francesco Facciolo
Rosario Amato
Lucia D'Antona
Massimo Rinaldi
Armando Felsani
Nicola Perrotti
Marco G Paggi
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2012
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/1756-9966-31-4

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Abstract

Background

Methods

Results

Conclusions

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