Abstract
Evaluation of tumor marker expression pattern that determines individual progression parameters is one of the major topics in molecular oncopathology research. This work represents research on expression analysis of several Ras-Ral associated signal transduction pathway proteins (Arf6, RalA, and BIRC5) in accordance with clinical criteria in nonsmall cell lung cancer patients. Using Western-blot analysis and RT-PCR Arf6, RalA, and BIRC5, expression has been analyzed in 53 nonsmall cell lung cancer samples of different origin. Arf6 protein expression was increased in 55% nonsmall cell lung cancer tumor samples in comparison with normal tissue. In the group of squamous cell lung cancer, increase of Arf6 expression was observed more often. RalA protein expression was decreased in comparison to normal tissue samples in 64% of nonsmall cell lung cancer regardless of morphological structure. Correlation between the decrease of RalA protein expression and the absence of regional metastases was revealed for squamous cell lung cancer. BIRC5 protein expression in tumor samples versus corresponding normal tissue was 1.3 times more often elevated in the squamous cell lung cancer group (in 76% tumor samples). At the same time, increase of BIRC5 expression was detected only in 63% of adenocarcinoma tumor samples. A statistically significant decrease (p = 0.015) of RalA protein expression and the increase (p = 0.049) of Arf6 protein expression in comparison with normal tissue was found in T1–2N0M0 and T1–2N1–2M0 groups of squamous cell lung cancer, respectively.
Similar content being viewed by others
Abbreviations
- AC:
-
adenocarcinoma
- LC:
-
lung cancer
- NSCLC:
-
nonsmall cell lung cancer
- SCLC:
-
squamous cell lung cancer
- RT-PCR:
-
reverse transcription polymerase chain reaction
References
Feig L.A. 2003. Ral-GTPases: Approaching their 15 minutes of fame. Trends Cell Biol. 13, 419–425.
Souza-Schorey C., Chavrier P. 2006. ARF proteins: Roles in membrane traffic and beyond. Nature Rev. Mol. Cell Biol. 7, 347–358.
Kahn R.A., Cherfils J., Elias M., Lovering R.C., Munro S., Schurmann A. 2006. Nomenclature for the human Arf family of GTP-binding proteins: ARF, ARL, and SAR proteins. J. Cell Biol. 172, 645–650.
Brown H.A., Gutowski S., Moomaw C.R., Slaughter C., Sternweis P. C. 1993. ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity. Cell. 75, 1137–1144.
Paris S., Beraud-Dufour S., Robineau S., Bigay J., Antonny B., Chabre M., Chardin P. 1997. Role of protein-phospholipid interactions in the activation of ARF1 by the guanine nucleotide exchange factor Arno. J. Biol. Chem. 272, 22221–22226.
Souza-Schorey C., Stahl P.D. 1995. Myristoylation is required for the intracellular localization and endocytic function of ARF6. Exp. Cell Res. 221, 153–159.
Xu L., Frankel P., Jackson D., Rotunda T., Boshans R.L., Souza-Schorey C., Foster D.A. 2003. Elevated phospholipase D activity in H-Rasbut not K-Ras-transformed cells by the synergistic action of RalA and Arf6. Mol. Cell Biol. 23, 645–654.
Foster D.A., Xu L. 2003. Phospholipase D in cell proliferation and cancer. Mol. Cancer Res. 1, 789–800.
Shi M., Zheng Y., Garcia A., Xu L., Foster D.A. 2007. Phospholipase D provides a survival signal in human cancer cells with activated H-Ras or K-Ras. Cancer Lett. 258, 268–275.
Zhao Y., Ehara H., Akao Y., Shamoto M., Nakagawa Y., Banno Y., Deguchi T., Ohishi N., Yagi K., Nozawa Y. 2000. Increased activity and intranuclear expression of phospholipase D2 in human renal cancer. Biochem. Biophys. Res. Commun. 278, 140–143.
Noh D.Y., Ahn S.J., Lee R.A., Park I.A., Kim J.H., Suh P.G., Ryu S.H., Lee K.H., Han J.S. 2000. Overexpression of phospholipase D1 in human breast cancer tissues. Cancer Lett. 161, 207–214.
Chen Y., Rodrik V., Foster D.A. 2005. Alternative phospholipase D/mTOR survival signal in human breast cancer cells. Oncogene. 24, 672–679.
Vaira V., Lee C.W., Goel H.L., Bosari S., Languino L.R., Altieri D. C. 2007. Regulation of survivin expression by IGF-1/mTOR signaling. Oncogene. 26, 2678–2684.
Altieri D. C. 2008. Survivin, cancer networks and pathway-directed drug discovery. Nature Rev. Cancer. 8, 61–70.
Krepela E., Dankova P., Moravcikova E., Krepelova A., Prochazka J., Cermak J., Schutzner J., Zatloukal P., Benkova K. 2009. Increased expression of inhibitor of apoptosis proteins, survivin and XIAP, in non-small cell lung carcinoma. Int. J. Oncol. 35, 1449–1462.
Vaishlia N.A., Zinov’eva M.V., Sass A.V., Kopantsev E.P., Vinogradova T.V., Sverdlov E.D. 2008. Increase of BIRC5 gene expression in non-small cell lung cancer and esophageal squamous cell carcinoma does not correlate with expression of genes SMAC/DIABLO and PML encoding its inhibitors. Mol. Biol. (Moscow). 42, 652–661.
Mehrotra S., Languino L.R., Raskett C.M., Mercurio A.M., Dohi T., Altieri D.C. 2010. IAP regulation of metastasis. Cancer Cell. 17, 53–64.
Smith S.C., Oxford G., Baras A.S., Owens C., Havaleshko D., Brautigan D.L., Safo M.K., Theodorescu D. 2007. Expression of Ral GTPases, their effectors, and activators in human bladder cancer. Clin. Cancer Res. 13, 3803–3813.
Tchevkina E., Agapova L., Dyakova N., Martinjuk A., Komelkov A., Tatosyan A. 2005. The small G-protein RalA stimulates metastasis of transformed cells. Oncogene. 24, 329–335.
Yin J., Pollock C., Tracy K., Chock M., Martin P., Oberst M., Kelly K. 2007. Activation of the Ral-GEF/Ral pathway promotes prostate cancer metastasis to bone. Mol. Cell Biol. 27, 7538–7550.
Oshita F., Ito H., Ikehara M., Ohgane N., Hamanaka N., Nakayama H., Saito H., Yamada K., Noda K., Mitsuda A., Kameda Y. 2004. Prognostic impact of survivin, cyclin D1, integrin beta1, and VEGF in patients with small adenocarcinoma of stage I lung cancer. Am. J. Clin. Oncol. 27, 425–428.
Kren L., Brazdil J., Hermanova M., Goncharuk V.N., Kallakury B.V., Kaur P., Ross J.S. 2004. Prognostic significance of anti-apoptosis proteins survivin and bcl-2 in non-small cell lung carcinomas: A clinicopathologic study of 102 cases. Appl. Immunohistochem. Mol. Morphol. 12, 44–49.
Hashimoto S., Onodera Y., Hashimoto A., Tanaka M., Hamaguchi M., Yamada A., Sabe H. 2004. Requirement for Arf6 in breast cancer invasive activities. Proc. Natl. Acad. Sci. U.S.A. 101, 6647–6652.
Li M., Wang J., Ng S.S., Chan C.Y., He M.L., Yu F., Lai L., Shi C., Chen Y., Yew D.T., Kung H.F., Lin M.C. 2009. Adenosine diphosphate-ribosylation factor 6 is required for epidermal growth factor-induced glioblastoma cell proliferation. Cancer. 115, 4959–4972.
Frasa M.A., Maximiano F.C., Smolarczyk K., Francis R.E., Betson M.E., Lozano E., Goldenring J., Seabra M.C., Rak A., Ahmadian M.R., Braga V.M. 2010. Armus is a Rac1 effector that inactivates Rab7 and regulates E-cadherin degradation. Curr. Biol. 20, 198–208
Monzo M., Rosell R., Felip E., Astudillo J., Sanchez J.J., Maestre J., Martin C., Font A., Barnadas A., Abad A. 1999. A novel anti-apoptosis gene: re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers. J. Clin. Oncol. 17, 2100–2104.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © A.V. Knizhnik, O.V. Kovaleva, K.K. Laktionov, V.V. Mochalnikova, A.V. Komelkov, E.M. Tchevkina, I.B. Zborovskaya, 2011, published in Molekulyarnaya Biologiya, 2011, Vol. 45, No. 2, pp. 307–315.
Rights and permissions
About this article
Cite this article
Knizhnik, A.V., Kovaleva, O.V., Laktionov, K.K. et al. Arf6, RalA, and BIRC5 protein expression in nonsmall cell lung cancer. Mol Biol 45, 275–282 (2011). https://doi.org/10.1134/S0026893310061032
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0026893310061032