Upregulated mRNA expression of mTOR in surgically resected early stage non-small cell lung carcinoma: a potential molecular targeted therapy

Muhammet Sayan; Ali Çelik; Şevki Mustafa Demiröz; Hacer İlke Önen; Nalan Akyürek; Ece Konaç; İsmail Cüneyt Kurul; Abdullah İrfan Taştepe

Araştırma Makalesi

Upregulated mRNA expression of mTOR in surgically resected early stage non-small cell lung carcinoma: a potential molecular targeted therapy

Yıl 2017, Cilt: 2 Sayı: 1, 5 - 10, 16.04.2017

Muhammet Sayan Ali Çelik Şevki Mustafa Demiröz Hacer İlke Önen Nalan Akyürek Ece Konaç İsmail Cüneyt Kurul Abdullah İrfan Taştepe

Öz

Background: Non-small cell lung cancer (NSCLC) comprises about 85%
of all lung cancers. Although many attempts for early detection and treatment,
prognosis of NSCLC is still poor. In
recent years the pathways and the genes that play role in lung cancer
development were researched widely. PI3K/AKT/MTOR which is thought to be
efficacious in the development of many cancer which controls the expression of
many genes playing an important role in cell proliferation, metastasis,
resistance to apoptosis and angiogenesis. Also the increase in CCND1 expression
was shown in several cancer types. The aim of this study is to search the mRNA
expression profile of AKT, MTOR and CCND1 genes which has been thought to
play role in NSCLC development, and their expression in different pathological
stages and histological types of the disease.

Materials and Methods: Forty-four NSCLC patients who didn’t get neoadjuvant
therapy were included in this study. The samples from tumor and matched normal
lung tissue were obtained from resection specimens (lobectomy or
pneumonectomy). Total cellular RNA was isolated from the samples. The mRNA
expression levels of AKT1, mTOR and CCND1 genes were measured by quantitative real-time polymerase
chain reaction (qPCR).

Results:
Our findings revealed a statistically significant increase of mTOR expression on mRNA levels (P < 0.05).
Although AKT and CCND1 expression slightly increased in malign tissues, these
changes in the expression were not significant (P > 0.05). The mRNA expression of mTOR was also
upregulated and it was statistically significant for early stage disease and
adenocarcinoma subtype (P < 0.05).

Conclusions: Inhibition of mTOR gene expression at mRNA level
might be potential target for future treatment strategies of NSCLC.

Anahtar Kelimeler

non-small cell lung cancer, mRNA expression, AKT1, mTOR, CCND1

Kaynakça

1. Deffebach ME, Humphrey L. Lung Cancer Screening. Surg Clin North Am 2015; 95: 967-78.
2. Hu Q, Zhou Y, Ying K, Ruan W. IGFBP, a novel target of lung cancer? Clin Chim Acta 2017; 466: 172-7.
3. Memmott RM, Dennis PA. The role of the Akt/mTOR pathway in tobacco carcinogen–induced lung tumorigenesis. Clin Cancer Res 2010; 16: 4-10.
4. Luo X, Zang X, Yang L, Huang J, Liang F, Rodriguez-Canales J, et al. Comprehensive Computational Pathological Image Analysis Predicts Lung Cancer Prognosis. J Thorac Oncol 2017; 12: 501-9.
5. Vooder T, Metspalu A. Investigating gene expression profile of non-small cell lung cancer. Cent Eur J Med 2011; 6: 608-15.
6. Bartholomeusz C, Gonzalez-Angulo AM. Targeting the PI3K signaling pathway in cancer therapy. Expert Opin Ther Targets 2012; 16: 121-30.
7. Fumarola C, Bonelli MA, Petronini PG, Alfieri RR. Targeting PI3K/AKT/mTOR pathway in non small cell lung cancer. Biochem Pharmacol 2014; 90:197-207.
8. Caron E, Ghosh S, Matsuoka Y, Ashton-Beaucage D, Therrien M, Lemieux S, et al. A comprehensive map of the mTOR signaling network. Mol Syst Biol 2010; 6: 453.
9. Liu Z, Wang L, Zhang LN, Wang Y, Yue WT, Li Q. Expression and clinical significance of mTOR in surgically resected non-small cell lung cancer tissues: a case control study. Asian Pac J Cancer Prev 2012; 13: 6139-44.
10. Seeliger H, Guba M, Kleespies A, Jauch KW, Bruns CJ. Role of mTOR in solid tumor systems: a therapeutical target against primary tumor growth, metastases, and angiogenesis. Cancer Metastasis Rev 2007; 26: 611-21.
11. Law M, Forrester E, Chytil A, Corsino P, Green G, Davis B, et al. Rapamycin disrupts cyclin/cyclin-dependent kinase/p21/proliferating cell nuclear antigen complexes and cyclin D1 reverses rapamycin action by stabilizing these complexes. Cancer Res 2006; 66: 1070-80.
12. Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 2002; 30: e36.
13. Langer CJ, Besse B, Gualberto A, Brambilla E, Soria JC. The evolving role of histology in the management of advanced non-small-cell lung cancer, J Clin Oncol 2010; 28: 5311-20.
14. Liloglou T, Bediaga NG, Brown BR, Field JK, Davies MP. Epigenetic biomarkers in lung cancer. Cancer Lett 2014; 342: 200-12.
15. Yue W, Wang X, Wang Y. The Relationship between the PI3K/Akt/mTOR Signal Transduction Pathway and Non-small Cell Lung Cancer. Zhongguo Fei Ai Za Zhi 2009; 12: 312-5.
16. Wang L, Xu S, Yue W, Zhao X, Zhang L, Wang Y. Expression and clinical significance of mTOR and PTEN in non-small cell lung cancer. Zhongguo Fei Ai Za Zhi 2010; 13: 717-21.
17. Li R, An SJ, Chen ZH, Zhang GC, Zhu JQ, Nie Q, et al. Expression of cyclin D1 splice variants is differentially associated with outcome in non-small cell lung cancer patients. Hum Pathol 2008; 39: 1792-801.
18. Matsubara H, Sakakibara K, Kunimitsu T, Matsuoka H, Kato K, Oyachi N, et al. Non-small cell lung carcinoma therapy using mTOR-siRNA. Int J Clin Exp Pathol 2012; 5: 119-25.

Yıl 2017, Cilt: 2 Sayı: 1, 5 - 10, 16.04.2017

Muhammet Sayan Ali Çelik Şevki Mustafa Demiröz Hacer İlke Önen Nalan Akyürek Ece Konaç İsmail Cüneyt Kurul Abdullah İrfan Taştepe

Öz

Kaynakça

1. Deffebach ME, Humphrey L. Lung Cancer Screening. Surg Clin North Am 2015; 95: 967-78.
2. Hu Q, Zhou Y, Ying K, Ruan W. IGFBP, a novel target of lung cancer? Clin Chim Acta 2017; 466: 172-7.
3. Memmott RM, Dennis PA. The role of the Akt/mTOR pathway in tobacco carcinogen–induced lung tumorigenesis. Clin Cancer Res 2010; 16: 4-10.
4. Luo X, Zang X, Yang L, Huang J, Liang F, Rodriguez-Canales J, et al. Comprehensive Computational Pathological Image Analysis Predicts Lung Cancer Prognosis. J Thorac Oncol 2017; 12: 501-9.
5. Vooder T, Metspalu A. Investigating gene expression profile of non-small cell lung cancer. Cent Eur J Med 2011; 6: 608-15.
6. Bartholomeusz C, Gonzalez-Angulo AM. Targeting the PI3K signaling pathway in cancer therapy. Expert Opin Ther Targets 2012; 16: 121-30.
7. Fumarola C, Bonelli MA, Petronini PG, Alfieri RR. Targeting PI3K/AKT/mTOR pathway in non small cell lung cancer. Biochem Pharmacol 2014; 90:197-207.
8. Caron E, Ghosh S, Matsuoka Y, Ashton-Beaucage D, Therrien M, Lemieux S, et al. A comprehensive map of the mTOR signaling network. Mol Syst Biol 2010; 6: 453.
9. Liu Z, Wang L, Zhang LN, Wang Y, Yue WT, Li Q. Expression and clinical significance of mTOR in surgically resected non-small cell lung cancer tissues: a case control study. Asian Pac J Cancer Prev 2012; 13: 6139-44.
10. Seeliger H, Guba M, Kleespies A, Jauch KW, Bruns CJ. Role of mTOR in solid tumor systems: a therapeutical target against primary tumor growth, metastases, and angiogenesis. Cancer Metastasis Rev 2007; 26: 611-21.
11. Law M, Forrester E, Chytil A, Corsino P, Green G, Davis B, et al. Rapamycin disrupts cyclin/cyclin-dependent kinase/p21/proliferating cell nuclear antigen complexes and cyclin D1 reverses rapamycin action by stabilizing these complexes. Cancer Res 2006; 66: 1070-80.
12. Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 2002; 30: e36.
13. Langer CJ, Besse B, Gualberto A, Brambilla E, Soria JC. The evolving role of histology in the management of advanced non-small-cell lung cancer, J Clin Oncol 2010; 28: 5311-20.
14. Liloglou T, Bediaga NG, Brown BR, Field JK, Davies MP. Epigenetic biomarkers in lung cancer. Cancer Lett 2014; 342: 200-12.
15. Yue W, Wang X, Wang Y. The Relationship between the PI3K/Akt/mTOR Signal Transduction Pathway and Non-small Cell Lung Cancer. Zhongguo Fei Ai Za Zhi 2009; 12: 312-5.
16. Wang L, Xu S, Yue W, Zhao X, Zhang L, Wang Y. Expression and clinical significance of mTOR and PTEN in non-small cell lung cancer. Zhongguo Fei Ai Za Zhi 2010; 13: 717-21.
17. Li R, An SJ, Chen ZH, Zhang GC, Zhu JQ, Nie Q, et al. Expression of cyclin D1 splice variants is differentially associated with outcome in non-small cell lung cancer patients. Hum Pathol 2008; 39: 1792-801.
18. Matsubara H, Sakakibara K, Kunimitsu T, Matsuoka H, Kato K, Oyachi N, et al. Non-small cell lung carcinoma therapy using mTOR-siRNA. Int J Clin Exp Pathol 2012; 5: 119-25.

Toplam 18 adet kaynakça vardır.

Ayrıntılar

Bölüm	Makaleler
Yazarlar	Muhammet Sayan Ali Çelik Bu kişi benim Şevki Mustafa Demiröz Bu kişi benim Hacer İlke Önen Bu kişi benim Nalan Akyürek Bu kişi benim Ece Konaç Bu kişi benim İsmail Cüneyt Kurul Bu kişi benim Abdullah İrfan Taştepe Bu kişi benim
Yayımlanma Tarihi	16 Nisan 2017
Yayımlandığı Sayı	Yıl 2017 Cilt: 2 Sayı: 1

Kaynak Göster

APA	Sayan, M., Çelik, A., Demiröz, Ş. M., Önen, H. İ., vd. (2017). Upregulated mRNA expression of mTOR in surgically resected early stage non-small cell lung carcinoma: a potential molecular targeted therapy. CURRENT THORACIC SURGERY, 2(1), 5-10.
AMA	Sayan M, Çelik A, Demiröz ŞM, Önen Hİ, Akyürek N, Konaç E, Kurul İC, Taştepe Aİ. Upregulated mRNA expression of mTOR in surgically resected early stage non-small cell lung carcinoma: a potential molecular targeted therapy. CTS. Nisan 2017;2(1):5-10.
Chicago	Sayan, Muhammet, Ali Çelik, Şevki Mustafa Demiröz, Hacer İlke Önen, Nalan Akyürek, Ece Konaç, İsmail Cüneyt Kurul, ve Abdullah İrfan Taştepe. “Upregulated MRNA Expression of MTOR in Surgically Resected Early Stage Non-Small Cell Lung Carcinoma: A Potential Molecular Targeted Therapy”. CURRENT THORACIC SURGERY 2, sy. 1 (Nisan 2017): 5-10.
EndNote	Sayan M, Çelik A, Demiröz ŞM, Önen Hİ, Akyürek N, Konaç E, Kurul İC, Taştepe Aİ (01 Nisan 2017) Upregulated mRNA expression of mTOR in surgically resected early stage non-small cell lung carcinoma: a potential molecular targeted therapy. CURRENT THORACIC SURGERY 2 1 5–10.
IEEE	M. Sayan, “Upregulated mRNA expression of mTOR in surgically resected early stage non-small cell lung carcinoma: a potential molecular targeted therapy”, CTS, c. 2, sy. 1, ss. 5–10, 2017.
ISNAD	Sayan, Muhammet vd. “Upregulated MRNA Expression of MTOR in Surgically Resected Early Stage Non-Small Cell Lung Carcinoma: A Potential Molecular Targeted Therapy”. CURRENT THORACIC SURGERY 2/1 (Nisan 2017), 5-10.
JAMA	Sayan M, Çelik A, Demiröz ŞM, Önen Hİ, Akyürek N, Konaç E, Kurul İC, Taştepe Aİ. Upregulated mRNA expression of mTOR in surgically resected early stage non-small cell lung carcinoma: a potential molecular targeted therapy. CTS. 2017;2:5–10.
MLA	Sayan, Muhammet vd. “Upregulated MRNA Expression of MTOR in Surgically Resected Early Stage Non-Small Cell Lung Carcinoma: A Potential Molecular Targeted Therapy”. CURRENT THORACIC SURGERY, c. 2, sy. 1, 2017, ss. 5-10.
Vancouver	Sayan M, Çelik A, Demiröz ŞM, Önen Hİ, Akyürek N, Konaç E, Kurul İC, Taştepe Aİ. Upregulated mRNA expression of mTOR in surgically resected early stage non-small cell lung carcinoma: a potential molecular targeted therapy. CTS. 2017;2(1):5-10.