Abstract:
:The hypoxia-inducible transcription factor, HIF-1, adapts cells to low oxygen tension. In addition to the activation of angiogenesis by induction of VEGF, HIF-1 may trigger hypoxia-induced growth arrest and apoptosis. The aim of this study was to analyze the overall effect of HIF-1 on tumor growth in a mouse model, employing human lung adenocarcinoma A549 cells. The A549 cells were transfected to overexpress HIF-1alpha. These cells displayed decreased proliferation, cell-cycle entry, colony formation in soft agar and elevated levels of apoptosis, when compared to control cells transfected with empty vector. The cells were employed in a tumor model by subcutaneous injection into CD-1 nude mice. Persistent overexpression of HIF1alpha and VEGF was demonstrated in these tumors. The HIF-1alpha-overexpressing tumors displayed less tumor growth when compared to tumors formed by control cells. Tumors derived from HIF-1alpha-overexpressing cells revealed an increase in apoptosis when compared to control tumors, in spite of a marked increase in vascular density. We conclude that in lung A549 cells, overexpression of HIF-1alpha negatively affects tumor growth due to decreased proliferation and increased apoptosis, despite augmented angiogenesis.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Savai R,Schermuly RT,Voswinckel R,Renigunta A,Reichmann B,Eul B,Grimminger F,Seeger W,Rose F,Hänze Jkeywords:
subject
Has Abstractpub_date
2005-08-01 00:00:00pages
393-400issue
2eissn
1019-6439issn
1791-2423journal_volume
27pub_type
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