Progressive and regressive fate of lens tumors correlates with subtle differences in transgene expression in gamma F-crystallin-SV40 T antigen transgenic mice.
Regulatory elements of the mouse gamma F-crystallin gene were used to derive transgenic mice expressing SV40 large T antigen in terminally differentiating fiber cells of the ocular lens. The resulting gamma F-crystallin-T antigen mice developed either malignant or regressive lens tumors in a strain-dependent fashion. Developmental and RNA analyses revealed that in both 'tumor-progressing' and 'tumor-regressing' mouse strains expression of the transgene blocked morphological differentiation of lens fibers without appreciably affecting gamma-crystallin gene expression, a marker of terminal lens fiber cell differentiation. Strain-dependent differences in tumorigenic outcome could be correlated with both subtle differences in transgene expression and the ability of tumor cells to escape from the normal confines of the lens. The results implicate the importance of cellular environment to malignant tumor development and provide insight into those features of normal lens ontogeny that may render the lens refractory to the development of spontaneous tumors.
Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
D M
DM
Bryce
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Q
Liu
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W
Khoo
L C
LC
Tsui
M L
ML
Breitman
D000818:Animals; D000831:Animals, Newborn; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis / Q000235:genetics*; D003459:Crystallins / Q000096:biosynthesis / Q000235:genetics*; D005134:Eye Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D007905:Lens Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D015183:Restriction Mapping; D013539:Simian virus 40 / Q000235:genetics; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming; D003459:Crystallins