The presence of Merkel cell polyomavirus is associated with deregulated expression of BRAF and Bcl-2 genes in non-small cell lung cancer.
Polyomaviruses such as BK virus (BKV), JC virus (JCV) and Merkel cell polyomavirus (MCPyV) are typically nononcogenic, although they have been detected in a variety of human neoplasms. The aim of our study was to determine the frequency of the most common polyomaviruses MCPyV, BKV and JCV as well as the gene expression profile of genes involved in oncogenesis including K-ras, BRAF, RKIP, Bax, Bcl-2, p53 and RB1 in a cohort of non-small cell lung cancer (NSCLC) patients. Real-time and nested polymerase chain reaction (PCR) were used to assess the presence of polyomaviruses DNA in tissue biopsies from 110 patients with primary NSCLC and 14 tissue specimens from macroscopically healthy sites of their lung. Real-time PCR was also used to determine the mRNA expression of K-ras, BRAF, RKIP, Bax, Bcl-2, p53 and RB1 in selected samples. Results showed that ten NSCLC specimens were positive for the presence of MCPyV DNA (10/110, 9.1%), whereas no control sample was tested positive for the virus. The MCPyV-positive samples were predominantly obtained from male smokers (9/10). BKV and JCV DNA were not detected either in lung tissues biopsies or the control specimens. Interestingly, gene expression analysis revealed increased mRNA and protein expression of BRAF gene in association with BRAF phosphorylation in the MCPyV-positive samples, whereas Bcl-2 gene expression was downregulated in the same type of samples. The detected MCPyV prevalence in NSCLC in combination with the deregulated expression of BRAF and Bcl-2 genes suggests that these events are likely to contribute to the pathogenesis of NSCLC.
Department of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion, Crete, Greece.
I
I
Lasithiotaki
K M
KM
Antoniou
S P
SP
Derdas
E
E
Sarchianaki
E K
EK
Symvoulakis
A
A
Psaraki
D A
DA
Spandidos
E N
EN
Stathopoulos
N M
NM
Siafakas
G
G
Sourvinos
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D059965:Merkel cell polyomavirus / Q000276:immunology* / Q000302:isolation & purification; D008875:Middle Aged; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics; D027601:Polyomavirus Infections / Q000235:genetics / Q000821:virology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012907:Smoking; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014412:Tumor Virus Infections / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
D004279:DNA, Viral; C117307:KRAS protein, human; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins