HIGH-LEVEL EXPRESSION OF HUMAN C-SRC CAN CAUSE A SPHERICAL MORPHOLOGYWITHOUT LOSS OF ANCHORAGE-DEPENDENT GROWTH OF NIH 3T3 CELLS

To investigate whether overexpression of human c-Src leads to cell rou nding in anchorage-dependent NIH3T3 fibroblasts, we have established c -Src-inducible cell lines using a lac repressor-operator system, RN1 c ells, which expressed c-Src at a high level after induction, exhibited a spherical morphology and ceased to grow in monolayer culture, RN1 c ells, however, exhibited neither focus-forming ability nor anchorage-i ndependent growth potential with or without induction, Induced RN1 c-S rc was phosphorylated at Ser(75) a previously reported spherical cell- associated site, and at Tyr(419). These data demonstrated for the firs t time that highly elevated human c-Src tyrosine kinase activity can c ause NIH 3T3 cells to have a spherical morphology without loss of anch orage-dependent growth. The inducible cell line should be useful to st udy the mechanism for cell rounding by c-Src. (C) 1997 Federation of E uropean Biochemical Societies.