Effects of the MYC oncogene antagonist, MAD, on proliferation, cell cycling and the malignant phenotype of human brain tumour cells.
To investigate how overexpression of MAD, an antagonist of MYC oncogenes influences the malignant phenotype of human cancer cells, an adenovirus vector system was used to transfer the human MAD gene (AdMAD) into human astrocytoma cells. Decreased growth potential of AdMAD-infected cells was evidenced by a decrease in [3H]thymidine incorporation, an increase in cell doubling time and alteration of cell-cycle distribution. Diminished malignant potential of AdMAD-infected cells was manifested by their loss of anchorage-independent growth in soft agar and by their inability, in general, to induce tumorigenesis in a xenograft animal model. These studies indicate that adenovirus constructs encoding MAD dramatically inhibit the proliferation and tumorigenicity of human astrocytoma cells and support the use of MAD for gene therapy of human tumours.
Chen
J
J
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.
Willingham
T
T
Margraf
L R
LR
Schreiber-Agus
N
N
DePinho
R A
RA
Nisen
P D
PD
D000818:Animals; D001254:Astrocytoma / Q000473:pathology*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D001932:Brain Neoplasms / Q000473:pathology*; D002051:Burkitt Lymphoma / Q000473:pathology; D002277:Carcinoma / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002448:Cell Adhesion; D002453:Cell Cycle; D002455:Cell Division; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000473:pathology; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000637:transplantation
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C499330:MAX protein, human; C079439:MXD1 protein, human; D046911:Macromolecular Substances; C499479:Mad protein, mouse; C067850:Myc associated factor X; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C068422:Max protein, mouse