ABSTRACT
Human T cell lymphotropic virus type 1 (HTLV-1) is associated with adult T cell leukemia/lymphoma (ATLL), a fetal malignant infection. Recently, HTLV-1 new asymptomatic carriers (ACs) have frequently been reported among blood donors. Reaching the profound concept of HTLV-1-associated molecular pathogenesis could result in finding novel therapeutic strategies. The current study aimed to determine leukemia-related signaling regulation in ATLL. Thirty participants were evaluated in 3 groups, including 10 ATLL patients, 10 ACs, and 10 normal controls. Blood samples were isolated without any chemotherapy history from ATLL patients. Also, blood samples were recovered from ACs and normal individuals. White blood cells isolation was done on the collected blood samples. After this, RNA was extracted from the prepared samples and used for the cDNA synthesis. TAX and HTLV-1 basic leucine zipper factor as viral genes and cellular genes, including MKP-1, EVI-1, JNK-1, FOXO-1, AKT-1, DEPTOR, MTOR, and JUN, were investigated using real-time PCR. The mean age of ATLL patients was 53.2 ± 7.32 years, and 9 (90%) were male. The EVI-1 and FOXO-1 expression levels were significantly associated with ATLL patients compared with the internal control. However, the significant differences in expression of other genes in the remaining groups were not seen. Discovering viral and cellular signaling pathways that regulate HTLV-1 transformation is essential. A novel therapeutic strategy for ATLL-regulating cellular signaling pathways in vivo could be considered. Therefore, clinical trials using activators and inhibitors of related cellular signaling pathways for cell therapy of ATLL are recommended. It is recommended that more investigation be conducted on FOXO-1 and EVI-1 to target these genes and reveal the molecular pathogenesis of ATLL.
ABSTRACT
OBJECTIVE: To examine the effect of HPV-16 E6 expression on the transcription of cellular genes, we used cDNA microarray in HPV-16 E6 transfected stable cancer cell lines. METHODS: Using cDNA microarray consisting of 1,024 genes, we have performed a systematic characterization of gene expression in A549E6 human lung adenocarcinoma and RC10.1 human colon adenocarcinoma cell lines stably expressing HPV-16 E6 gene. The up-regulated and down-regulated genes were classified into the different functional categories; oncogenes, apoptosis, cell cycle, signal transduction, gene regulation, immune response, cell adhesion, protein transport, metabolism, redox control and angiogenesis. RESULTS: Among 1,024 known genes and ESTs (expressed sequence tags) tested, we found 27 up- regulated and 43 down-regulated genes in A549E6 (HPV-16 E6) compared to A549. The major up-regulated genes were as follows. GTPase-activating protein Rho 4, transcription factor D2, IKAROS, integrin-alpha 6, cadherin 11, ephrin-beta 2, RAN binding protein 2, branched-chain amino transferase 2. The major down-regulated genes were as follows. K-ras 2, CDC (cell division cycle) 37, CDC16, CDC7L1, IRF3, interferon-gamma-inducible protein 30, cadherin 6, desmoglein 1, desmocollin 2, endothelin 2. Also, we found 48 up-regulated and 34 down-regulated genes in RC10.1 (HPV-16 E6) compared to RKO. The major up-regulated genes were as follows. Colon cancer familial nonpolyposis type 1 (COCA 1), Bcl 2, jagged 1, MAP2K6, E2F1, ephrin receptor-beta 2, ephrin-beta 2, desmoglein 1, transforming growth factor-beta 3. The major down-regulated genes were as follows. KIT, Rad51C, Bcl 2 antagonist killer 1, STAT 4, epidermal growth factor receptor, high mobility group protein 2, cadherin 11, cadherin 12, cadherin 3, integrin-alpha 1, intergrin-alpha 8, chromosome segregation 1-like. CONCLUSION: Various expression patterns of cellular genes by HPV-16 E6 could be wholy grasped and classified into different functional groups using both cell line system stably expressed HPV-16 E6 and cDNA microarray analysis. These analysis methods must be helpful to understand multiple effects of a specific gene on cellular genes in a short period.