PROGRESSIVE AND REGRESSIVE FATE OF LENS TUMORS CORRELATES WITH SUBTLEDIFFERENCES IN TRANSGENE EXPRESSION IN GAMMA-F-CRYSTALLIN-SV40 T-ANTIGEN TRANSGENIC MICE

Regulatory elements of the mouse gammaF-crystallin gene were used to d erive transgenic mice expressing SV40 large T antigen in terminally di fferentiating fiber cells of the ocular lens. The resulting gammaF-cry stallin-T antigen mice developed either malignant or regressive lens t umors in a strain-dependent fashion. Developmental and RNA analyses re vealed that in both 'tumor-progressing' and 'tumor-regressing' mouse s trains expression of the transgene blocked morphological differentiati on of lens fibers without appreciably affecting gamma-crystallin gene expression, a marker of terminal lens fiber cell differentiation. Stra in-dependent differences in tumorigenic outcome could be correlated wi th both subtle differences in transgene expression and the ability of tumor cells to escape from the normal confines of the lens. The result s implicate the importance of cellular environment to malignant tumor development and provide insight into those features of normal lens ont ogeny that may render the lens refractory to the development of sponta neous tumors.