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Identification of genes responsible for tumor induction with avian retroviruses subgroup J
Gašpareková, Mária ; Pečenka, Vladimír (advisor) ; Španielová, Hana (referee)
Retroviruses are viruses which are able to integrate to genome of host cell. Nonrandom integration of provirus near or inside some cellular genes may result in their deregulation, activation or silencing. This can later lead to cell transformation and tumor formation. This thesis discusses identification of viral integration sites (VIS) and common integration sites (CIS) in tumors originating from different organs (mostly kidneys, lungs and liver) with using mostly avian retroviruses subgroup J, specifically first natural isolate HPRS-103 and laboratory made virus MAV-J, which was made by replacing gene envB by envJ. Infection was made in ovo using chicken breeds Brown Leghorn and White Leghorn and tumors were isolated from 8 to 28 weeks after infection. For molecular analyses was used inverse PCR method and sequencing. From 74 molecularly analyzed tumors there was detected 373 VIS and 6 CIS with statistical significance over 2.10-2 . Gene with the highest number of hits was FRK (14 times), then TERT (5 times), CTDSPL (5 times), EGFR/ERBB1 (3 times), MYB (3 times) and MYC (3 times). Except 6 CIS there were other genes found, which had smaller statistical significance. Keywords: retrovirus, insertional mutagenesis, subgroup J, oncogenesis, oncogenes, MAV-J, HPRS-103, proviral integration sites, tumors
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Oncoretroviruses: tumor transformation mechanisms of hematopoietic cells resulting in leukaemia
Gašpareková, Mária ; Bendová, Michaela (advisor) ; Mrvová, Silvia (referee)
HTLV-1 and FeLV are retroviruses, which are able to transform host cells and cause cancer, mostly leukemia, in infected organism. Belonging to Retroviridae family and both using very similar genome, these viruses developed different ways to reach transformation of infected cells. While FeLV uses insertional activation close to cellular proto-oncogenes in order to regulate transcription of these genes or carries cellular oncogene in its genome, HTLV-1 codes viral proteins which are able to regulate many processes of the cell. One of these proteins is Tax, which regulates many events in the cell, such as signalization, cell cycle, apoptosis and others. Another protein responsible for oncogenesis is HBZ, which is transcribed from antisense strand of proviral DNA. In the end HTLV-1 and FeLV strategies causing cancer are compared with some other leukemic retroviruses in order to show, that molecular strategies described on examples of HTLV-1 and FeLV are more or less common also for other oncogenic retroviruses. Key words: HTLV-1, FeLV, transformation, leukaemia, tumor, oncogene
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