Transforming activity of a newly cloned androgen-induced growth factor.
Our previous study demonstrated that androgen-dependent growth of mouse mammary carcinoma cells (SC-3) was mediated through an induction of heparin-binding growth factor, termed as androgen-induced growth factor (AIGF). Here, we report that NIH3T3 cells stably transfected with AIGF expression vector exhibit the abilities of tumor formation in nude mice, focus formation in monolayer culture and colony formation in soft agar. Thus, this newly cloned growth factor can be categorized as an oncogene. In addition, androgen-induced enhancement of DNA synthesis in SC-3 cells can be blocked by simultaneous incubation with AIGF antisense oligonucleotides. The possibility is also addressed that AIGF exerts its biological activity through an interaction with fibroblast growth factor (FGF) receptor. Transfection of expression vector encoding a variant form of FGF receptor-1 cloned from SC-3 cells into FGF receptor-negative L6 cells results in AIGF-dependent inhibition of differentiation. These results demonstrate that the ability of androgen to elicit transformed phenotype of SC-3 cells is mediated through AIGF induction and its interaction with FGF receptor-1.
Kouhara
H
H
Department of Medicine III, Osaka University Medical School, Japan.
Koga
M
M
Kasayama
S
S
Tanaka
A
A
Kishimoto
T
T
Sato
B
B
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D005822:Genetic Vectors; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009857:Oncogenes / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D014162:Transfection
C496457:Fgf8 protein, mouse; D006133:Growth Substances; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D017468:Receptors, Fibroblast Growth Factor; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D004247:DNA