Simultaneous suppression of progression marker genes in the highly malignant human melanoma cell line BLM after transfection with the adenovirus-5 E1A gene.
The highly metastatic human melanoma cell line BLM was transfected with the E1A or E1A + E1B regions of adenovirus 5 (Ad5). A series of progression markers, correlated with the malignant phenotype of parental BLM (including calcyclin, thymosin beta 10, plasminogen activator inhibitors types 1 and 2, urokinase type and tissue type plasminogen activators, vimentin, tissue type transglutaminase, and interleukin-6), was collectively repressed in the transfectants, whereas several control genes were not affected or even induced. The apparently coordinate repression of a set of markers by the same regulator gene, Ad5 E1A in this case, suggests the existence of one pathway under the control of a main switch and predicts that one or more as yet unidentified cellular master genes normally exert this function. A reduced oncogenicity was observed after subcutaneous inoculation of the E1A transfectants into nude mice and provides additional evidence in support of a tumor suppressor function of Ad5 E1A.
van Groningen
J J
JJ
Department of Biochemistry, University of Nijmegen, The Netherlands.
Cornelissen
I M
IM
van Muijen
G N
GN
Bloemers
H P
HP
Swart
G W
GW
D017500:Adenovirus E1A Proteins / Q000235:genetics; D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005814:Genes, Viral; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008545:Melanoma / Q000235:genetics* / Q000276:immunology / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D013489:Suppression, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D014408:Biomarkers, Tumor; D015850:Interleukin-6