%0 Journal Article
%T Transformation and scattering activities of the receptor tyrosine kinase RON/Stk in rodent fibroblasts and lack of regulation by the jaagsiekte sheep retrovirus receptor, Hyal2
%A A Dusty Miller
%A Neal S Van Hoeven
%A Shan-Lu Liu
%J BMC Cancer
%D 2004
%I BioMed Central
%R 10.1186/1471-2407-4-64
%X Due to difficulty with reproducibility of the transformation assay in BEAS-2B cells, we have used more tractable rodent fibroblast models to further study Hyal2 modulation of RON/Stk transforming activity and potential effects of Hyal2 on RON/Stk activation by its natural ligand, macrophage stimulating protein (MSP).We did not detect transformation of NIH 3T3 cells by plasmids expressing RON or Stk, but did detect transformation of 208F rat fibroblasts by these plasmids at a very low rate. We were able to isolate 208F cell clones that expressed RON or Stk and that showed changes in morphology indicative of transformation. The parental 208F cells did not respond to MSP but 208F cells expressing RON or Stk showed obvious increases in scattering/transformation in response to MSP. Human Hyal2 had no effect on the basal or MSP-induced phenotypes of RON-expressing 208F cells, and human, mouse or rat Hyal2 had no effect on the basal or MSP-induced phenotypes of Stk-expressing 208F cells.We have shown that RON or Stk expression in 208F rat fibroblasts results in a transformed phenotype that is enhanced by addition of the natural ligand for these proteins, MSP. Hyal2 does not directly modulate the basal or MSP-induced RON/Stk activity, although it is possible that adaptor proteins might mediate such signaling in other cell types.JSRV is an acutely oncogenic retrovirus that can induce lung tumors in newborn sheep in as little as 10 days [1]. Unlike most acutely oncogenic retroviruses, JSRV does not carry a host cell-derived oncogene. Instead, expression of the native viral Env protein is sufficient to transform cultured cells and is likely to be the active oncogene in animals [2-5]. The only other examples of such retroviruses are enzootic nasal tumor virus, a close relative of JSRV that encodes a similar transforming Env protein [6,7]; avian hemangioma virus [8], which expresses an Env protein that can induce cell proliferation in cultured cells [9]; and spleen focus-forming
%U http://www.biomedcentral.com/1471-2407/4/64