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M94B0792.TXT
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1994-11-11
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Document 0792
DOCN M94B0792
TI Proliferation of leiomyosarcoma cell lines is inhibited in vitro by
antisense oligonucleotides directed against the insulin growth factor
Type I receptor (Meeting abstract).
DT 9412
AU Hirschfeld S; Helman LJ; Pediatric Branch, NCI, Bethesda, MD
SO Proc Annu Meet Am Assoc Cancer Res; 35:A1543 1994. Unique Identifier :
AIDSLINE ICDB/94603229
AB Smooth muscle proliferation can lead to a variety of pathologic
conditions, including benign (leiomyoma) and malignant (leiomyosarcoma;
LMS). Published studies have shown that smooth muscle cell proliferation
can be enhanced by insulin growth factor I (IGF-I), and that surgical
specimens of LMS contain RNA transcripts for IGF-II. In addition, in
children with HIV infection, there is an unusually high incidence of
smooth muscle tumors compared to uninfected children. The present study
was performed to see if the IGF signaling pathway could regulate
proliferation of LMS cell lines. Cell lines were tested for the presence
of IGF RNA transcripts by northern blotting using cloned fragments of
IGF-I and IGF-II as probes. In contrast to the reports on surgical
specimens, none of the lines showed detectable levels of IGF-II RNA, and
only minimally detectable levels of IGF-I RNA. Monoclonal antibody
directed against the Type I receptor showed a 15% decrease in growth
rate for one line, and had no effect on the others. Using
oligonucleotide sequences from two different regions of the IGF type I
receptor, we were able to show a 30-50% decrease in the rate of
proliferation, with a peak effect between 48 and 72 hours after the
addition of the oligonucleotides to the medium. A combination of
sequences was more effective on a molar basis than either sequence
alone. Alterations in growth rate were not observed using sequences
directed against the epidermal growth factor receptor. These results
suggest a role for the IGF Type I receptor in the regulation of LMS
proliferation, which may have therapeutic implications.
DE Human Leiomyosarcoma/*PATHOLOGY/*THERAPY Oligonucleotides,
Antisense/PHARMACOLOGY Receptors, Insulin-Like-Growth Factor I/*DRUG
EFFECTS/*METABOLISM Receptors, Insulin-Like-Growth-Factor II/METABOLISM
Tumor Cells, Cultured MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).