TUMOR-INDUCTION BY A TRANSFORMATION-DEFECTIVE POLYOMA-VIRUS MUTANT BLOCKED IN SIGNALING THROUGH SHC

Transformation of cells in culture by polyoma virus requires integrati on of signals downstream of middle T-Shc and middle T-phosphatidylinos itol 3-kinase interactions, but the same is not true for induction of tumors In the mouse, Thus, a middle T mutant defective in transformati on and blocked in binding Shc is able to induce a broad spectrum of tu mors after inoculation into newborn mice, The ''tumor profile'' induce d by the mutant shuns enhancement of tumors at some sites and reductio ns at others but otherwise resembles that induced by the wild-type vir us. A nontransforming double-mutant blocked in binding phosphatidylino sitol 3-kinase as well as Shc is severely affected but still induces s ome tumors, These results show that pathways that must cooperate to in duce full transformation of cells in vitro can act independently and a re to a large extent redundant in tumor induction.