title: v-erbA oncogene induces invasiveness and anchorage-independent growth in cultured glial cells by mechanisms involving platelet-derived growth factor.
abstract: The v-erbA oncogene coding for a mutated form of the thyroid hormone (T3) receptor (TR alpha 1) increased the invasion capacity of the mouse B3.1 glial cell line. This effect was mediated by the induction of platelet-derived growth factor (c-sis/PDGF B), as shown by its inhibition using an anti-PDGF BB antibody. Also, the low invasion capacity of parental B3.1 and c-erbA-expressing cells (B3.1 + TR alpha 1) was enhanced by exogenously added PDGF BB. This effect was independent of the growth-promoting activity of PDGF and unrelated to the secretion of metalloproteinases. All three cell types (parental B3.1, B3.1 + v-erbA, and B3.1 + TR alpha 1) secreted similar high levels of the M(r) 72,000 collagenase IV (A) independently of PDGF. Anchorage-independent cell growth was also enhanced by v-erbA; B3.1 + v-erbA cells but neither parental B3.1 nor B3.1 + TR alpha 1 cells formed foci in soft agar. The effect of v-erbA only happened in the presence of serum, suggesting that some serum factor(s) cooperate with PDGF to overcome the anchorage dependence of B3.1 + v-erbA cells. Supporting this, high doses of exogenous PDGF were much less efficient than serum, and the addition of an anti-PDGF BB antibody blocked only partially the effect of serum. Basic fibroblast growth factor was found to cooperate with PDGF to abolish anchorage dependence. Moreover, B3.1 + v-erbA cells detached and grew in suspension when cultured on plastic dishes. Interestingly, the transformation-competent c-jun and fra-1 oncogenes were induced by v-erbA in serum-free medium and are candidates to mediate v-erbA effects. In summary, our results show that v-erbA induces transformation parameters in the glial B3.1 cell line via an increase in c-sis/PDGF B and probably other mechanisms, suggesting a role for (autocrine) PDGF stimulation in glial cell transformation.
authors.affiliation: Instituto de Investigaciones Biomedicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Llanos
authors.forename: T
authors.initials: T
authors.lastname: Iglesias
authors.forename: H H
authors.initials: HH
authors.lastname: Riese
authors.forename: T
authors.initials: T
authors.lastname: Garrido
authors.forename: C
authors.initials: C
authors.lastname: Caelles
authors.forename: A
authors.initials: A
authors.lastname: Muñoz
mesh_terms: D000818:Animals; D000077214:Becaplermin; D001769:Blood; D002448:Cell Adhesion; D002452:Cell Count; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D017364:Collagenases / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D018776:Genes, erbA / Q000502:physiology*; D016758:Genes, jun / Q000235:genetics; D051379:Mice; D009361:Neoplasm Invasiveness; D009457:Neuroglia / Q000166:cytology* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000032:analysis; D011988:Receptors, Thyroid Hormone / Q000235:genetics; D014284:Triiodothyronine; D000099169:Fos-Related Antigen 1
chemical_list: D000077214:Becaplermin; D017364:Collagenases; D016222:Fibroblast Growth Factor 2; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D000099169:Fos-Related Antigen 1