The v-erbA oncogene blocks expression of alpha2/beta1 integrin a normal inhibitor of erythroid progenitor proliferation.
T2EC are chicken erythrocytic progenitors that balance between self-renewal and differentiation as a function of response to specific growth factors. Their transformation by the v-erbA oncogene locks them into the self-renewal program. We show here that the expression of the VLA-2 integrin alpha2 subunit mRNA is downregulated by v-erbA and that VLA-2 engagement and clustering, brought about by treatment with an alpha2-specific antibody or by culture on the VLA-2 ligand collagen I, inhibits T2EC proliferation. From competition studies using antibodies, VLA-2 was shown to be involved in the collagen-induced response. While engagement of VLA-2 inhibited proliferation, it was not sufficient to induce differentiation. The transformation of T2EC by v-erbA decreased their interaction with collagen I and the VLA-2 brake on cell proliferation, which may account for the increased proliferation potential of transformed erythrocytic progenitors and for their shedding into the blood of infected chickens. Our data suggest that the interaction between erythroid progenitors and collagen, mediated by VLA-2, play a major role in the control of erythropoiesis in vitro and that this pathway is a target of the v-erbA oncogene.
Mey
Anne
A
Laboratoire de Biologie Moléculaire et Cellulaire, CNRS UMR 5665, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69008 Lyon, France.
Gandrillon
Olivier
O
McNagny
Kelly M
KM
Clegg
Dennis O
DO
Samarut
Jacques
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002413:Cations, Divalent; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D002645:Chickens; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D015536:Down-Regulation; D004912:Erythrocytes / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics*; D018774:Oncogene Proteins v-erbA / Q000235:genetics / Q000378:metabolism*; D038981:Receptors, Collagen
D000911:Antibodies, Monoclonal; D002413:Cations, Divalent; D024042:Collagen Type I; D005353:Fibronectins; D016023:Integrins; D018774:Oncogene Proteins v-erbA; D038981:Receptors, Collagen; D003094:Collagen