Arf6, RalA, and BIRC5 protein expression in nonsmall cell lung cancer

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.

[1]  Y. Onodera,et al.  Requirement for Arf6 in breast cancer invasive activities. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[2]  K. Kelly,et al.  Activation of the RalGEF/Ral Pathway Promotes Prostate Cancer Metastasis to Bone , 2007, Molecular and Cellular Biology.

[3]  D. A. Foster,et al.  Phospholipase D in cell proliferation and cancer. , 2003, Molecular cancer research : MCR.

[4]  D. Theodorescu,et al.  Expression of Ral GTPases, Their Effectors, and Activators in Human Bladder Cancer , 2007, Clinical Cancer Research.

[5]  Y. Akao,et al.  Increased activity and intranuclear expression of phospholipase D2 in human renal cancer. , 2000, Biochemical and biophysical research communications.

[6]  E. Felip,et al.  A novel anti-apoptosis gene: Re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  P. Zatloukal,et al.  Increased expression of inhibitor of apoptosis proteins, survivin and XIAP, in non-small cell lung carcinoma. , 2009, International journal of oncology.

[8]  C. D’Souza-Schorey,et al.  Elevated Phospholipase D Activity in H-Ras- but Not K-Ras-Transformed Cells by the Synergistic Action of RalA and ARF6 , 2003, Molecular and Cellular Biology.

[9]  David A Foster,et al.  Alternative phospholipase D/mTOR survival signal in human breast cancer cells , 2005, Oncogene.

[10]  L. Feig Ral-GTPases: approaching their 15 minutes of fame. , 2003, Trends in cell biology.

[11]  Jide Wang,et al.  Adenosine diphosphate‐ribosylation factor 6 is required for epidermal growth factor‐induced glioblastoma cell proliferation , 2009, Cancer.

[12]  L. Languino,et al.  IAP regulation of metastasis. , 2010, Cancer cell.

[13]  V. Vaira,et al.  Regulation of survivin expression by IGF-1/mTOR signaling , 2007, Oncogene.

[14]  B. Antonny,et al.  Role of Protein-Phospholipid Interactions in the Activation of ARF1 by the Guanine Nucleotide Exchange Factor Arno* , 1997, The Journal of Biological Chemistry.

[15]  H. Brown,et al.  ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity , 1993, Cell.

[16]  M. Ahmadian,et al.  Armus Is a Rac1 Effector that Inactivates Rab7 and Regulates E-Cadherin Degradation , 2010, Current Biology.

[17]  M. Shi,et al.  Phospholipase D provides a survival signal in human cancer cells with activated H-Ras or K-Ras. , 2007, Cancer letters.

[18]  S. Munro,et al.  Nomenclature for the human Arf family of GTP-binding proteins: ARF, ARL, and SAR proteins , 2006, The Journal of cell biology.

[19]  Crislyn D'Souza-Schorey,et al.  ARF proteins: roles in membrane traffic and beyond , 2006, Nature Reviews Molecular Cell Biology.

[20]  Y. Kameda,et al.  Prognostic Impact of Survivin, Cyclin D1, Integrin β1, and VEGF in Patients With Small Adenocarcinoma of Stage I Lung Cancer , 2004, American journal of clinical oncology.

[21]  N. Dyakova,et al.  The small G-protein RalA stimulates metastasis of transformed cells , 2005, Oncogene.

[22]  D. Altieri Survivin, cancer networks and pathway-directed drug discovery , 2008, Nature Reviews Cancer.

[23]  D. Noh,et al.  Overexpression of phospholipase D1 in human breast cancer tissues. , 2000, Cancer letters.

[24]  E. D. Sverdlov,et al.  [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]. , 2008, Molekuliarnaia biologiia.