REDUCTION IN FIBRONECTIN EXPRESSION AND ALTERATION IN CELL MORPHOLOGYARE COINCIDENT IN NIH3T3 CELLS EXPRESSING A MUTANT E2F1 TRANSCRIPTIONFACTOR

Fibronectin within the extracellular matrix plays a role in cell attac hment, spreading, and shape, while it also affects aspects of cell pro liferation. Transcription factors such as E2F1 are also known to regul ate cell shape and cell proliferation. Yet, to date no linkage has bee n established between fibronectin expression and E2F1. We show here th at cells constitutively expressing a mutant E2F1 protein (E2F1d87) pro duce reduced amounts of fibronectin mRNA and protein. The altered expr ession of fibronectin seen in the E2F1d87 expressing cells is due, in part, to a reduction in transcription from the fibronectin promoter. P roviding exogenous fibronectin, but not Type I collagen or laminin, as a substrate for cell adhesion is sufficient to revert the altered mor phology and reestablish actin-containing microfilaments lost in the mu tant cell line. An additional characteristic of the cells expressing t he mutant E2F1 is that they demonstrate slow growth and a doubling in S phase duration. While providing exogenous fibronectin as an adhesion substrate did not shorten the S phase duration in the mutant line, it did significantly shorten the S phase duration in the parental NIH3T3 cell line, implicating a role for the extracellular matrix in regulat ing S phase transit in normal cells. (C) 1997 Academic Press.