The effect of an antisense expression plasmid to the IGF-1 receptor on hamster mesothelioma proliferation.
We have evaluated the effect of antisense IGF receptor transcripts on the proliferation and tumorigenicity in an SV40-induced, immunocompetent hamster mesothelioma model (H9A). Expression of IGF-1 and IGF-1 receptor (IGF-1 R) genes was identified from H9A RNA using RT-PCR and Northern blot analysis. H9A cells were electroporated with inducible expression vectors (under the transcriptional control of heat shock promotor HSP70) containing a cDNA fragment corresponding to bp 1-309 of IGF-1 R in the sense or antisense orientation to generate the respective clones A3 sense or B9 antisense. At 39 degrees C, the B9 antisense transfectants demonstrated significantly less proliferation than A3 sense transfectants (p2 < 0.02). At 34 degrees C, cell growth of A3 sense and B9 antisense transfected cells was not significantly different. The A3 sense clones resulted in greater numbers of tumours in vivo compared to the B9 antisense clone (p2 = 0.0001). The inhibitory effect of IGF-1R antisense transcripts on hamster mesothelioma demonstrated in this study by decreased growth and tumorigenicity in vitro and in vivo may have implications for the therapy of human mesothelioma.
Pass
H I
HI
Thoracic Oncology Section, NCI/NIH, Bethesda, MD, USA.
Mew
D J
DJ
Carbone
M
M
Donington
J S
JS
Baserga
R
R
Steinberg
S M
SM
D000818:Animals; D001195:Asbestosis / Q000150:complications; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D006224:Cricetinae; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D008654:Mesothelioma / Q000209:etiology / Q000473:pathology* / Q000821:virology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010957:Plasmids; D010997:Pleural Neoplasms / Q000209:etiology / Q000473:pathology* / Q000821:virology*; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000502:physiology*; D013539:Simian virus 40 / Q000302:isolation & purification; D014407:Tumor Cells, Cultured
D018840:HSP70 Heat-Shock Proteins; D016376:Oligonucleotides, Antisense; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1