A truncated RARα co-operates with the v-erbB oncogene to transform early haematopoietic progenitors in vitro and in vivo

Abstract

We have shown recently that a retrovirus vector expressing a natural mutant form of the PML-RAR alpha protein characteristic of human acute promyelocytic leukaemia can transform early chicken hematopoietic progenitors (Altabef et al., 1996). Neither truncated PML nor truncated RAR alpha alone could induce transformation which suggest that the two domains should cooperate for the oncogenicity of the fusion product. To further investigate the mechanisms of this co-operation, we have tested whether a truncated RAR alpha could cooperate with the v-erbB oncogene. This oncogene has previously been shown to co-operate with the rearranged thyroid hormone receptor, v-erbA, to transform erythrocytic progenitors. We show that v-erbB and a truncated RAR alpha co-operate when expressed simultaneously as independent products to transform very early chicken haematopoietic cells close to pluripotent stage. In addition, we show that v-erbB alters transcriptional abilities of RAR alpha by both enhancing its effects on RARE and reducing those on AP-1. Therefore, RAR alpha is able to co-operate with different kinds of proteins to induce transformation of early haematopoietic cells. This strongly suggests that RAR alpha are involved in the differentiation commitment of early haematopoietic progenitors during the normal process of haematopoietic differentiation. These data bring new insights in the mechanisms of oncogenic transformation by rearranged RAR alpha.

TGF-β cooperates with TGF-α to induce the self–renewal of normal erythrocytic progenitors: evidence for an autocrine mechanism

“…This suggests that T2EC cultures contained cells somewhere in between multipotent progenitors and mature CFU‐Es. This pattern of antigen expression is very reminiscent of haematopoietic chicken cells transformed by retroviruses expressing PML–RARα or ΔRARα plus v‐erbB (Altabef et al ., 1996, 1997).…”

Primary structure and expression of a naturally truncated human P2X ATP receptor subunit from brain and immune system

“…In any case, as has been described in other classes of multimeric integral proteins, i.e. the neurotrophin receptors [28], the steroid receptors [29] and voltage-gated K channels [30], the regulatory effect of a dominant negative truncated hP2X 5 R subunit on human heteromeric ATP-gated channels remains to be investigated.…”

True

“…The pRSV-Jun and pSV-Fos expression vectors and Coll-p(−517/+63) interstitial collagenase-CAT gene reporter vector were previously described. 52 A constitutive luciferase-expression vector (generously provided by Dr C Gazin, Paris, France) was used to normalize transfection efficiency.…”