Proliferation of leiomyosarcoma cell lines is inhibited in vitro by antisense oligonucleotides directed against the insulin growth factor Type I receptor (Meeting abstract).

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Proliferation of leiomyosarcoma cell lines is inhibited in vitro by antisense oligonucleotides directed against the insulin growth factor Type I receptor (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 35:A1543 1994. Unique Identifier : AIDSLINE ICDB/94603229
Hirschfeld S; Helman LJ; Pediatric Branch, NCI, Bethesda, MD

Abstract: 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.

Keywords: 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 ABSTRACT
941230
M94C4329

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