The role of transforming growth factor alpha production and XXXX overexpression in induction of tumorigenicity of lung epithelial cells.

@entity1 @entity70703 @entity19 @entity5 @entity470 @entity7790 @entity2220 @entity1722
Over-expression of @entity1722 is associated with shortened survival of @entity1 with @entity2220 . We demonstrated that @entity1 lung epithelial cells, overexpressing @entity1722 , formed @entity5 in @entity19 only when high levels of transforming growth factor (TGF)-alpha were produced (E6T cells). To define the role that @entity7790 production played in induction of tumorigenicity, a non-tumorigenic @entity7790 -negative clone of @entity1722 overexpressing cells (E2 cells) was transfected with an expression vector for @entity7790 (E2alpha cells). Transfected clones produced @entity7790 at 11-25% of the level produced by the E6T cell line. Tumorigenic E6T cells transfected with a @entity7790 antisense vector (E6TA cells) expressed only 6% of the @entity7790 level of the parental cells. Clones of @entity70703 , E6TA, E2 and E2alpha were inoculated into athymic @entity19 to measure tumorigenic potential. E6T cells formed @entity5 with a 70% efficiency. E2, E6TA and E2alpha cells failed to form @entity5 . The levels of @entity470 were similar in non-tumorigenic E2 and tumorigenic E6T cells but higher in E2alpha and E6TA cells, and @entity1722 were greatly overexpressed in an E2alpha clone. In vitro, @entity1722 co-immunoprecipitated with @entity470 in lysates of unstimulated @entity70703 and E2alpha @entity7790 -producing cells, indicating that the lower @entity7790 levels were sufficient to induce in vitro heterodimerization. These studies suggest that induction of the tumorigenic phenotype depends on achieving a threshold level of @entity7790 sufficient to activate downstream signalling by @entity1722 containing active heterodimers.
