@entity19 expressing MyrAkt from a proximal @entity29939 promoter construct develop @entity704 at an early age, whereas @entity19 expressing constitutively active @entity29939 -AktE40K develop primarily @entity5 of the peripheral lymphoid organs later in life. The thymus of 6- to 8-week-old MyrAkt @entity19 is normal in size but contains fewer, larger cells than the thymus of nontransgenic control and AktE40K @entity19 . Earlier studies had shown that cell size and cell cycle are coordinately regulated. On the basis of this finding, and our observations that the oncogenic potential of @entity1994 correlates with its effect on cell size, we hypothesized that mechanisms aimed at maintaining the size of the thymus dissociate cell size and cell cycle regulation by blocking MyrAkt-promoted G(1) progression and that failure of these mechanisms may promote cell proliferation resulting in an enlarged neoplastic thymus. To address this hypothesis, we examined the cell cycle distribution of freshly isolated and cultured thymocytes from transgenic and nontransgenic control @entity19 . The results showed that although neither transgene alters cell cycle distribution in situ, the MyrAkt transgene promotes G(1) progression in culture. Freshly isolated MyrAkt thymocytes express high levels of cyclins D2 and E and @entity11953 but lower than normal levels of @entity43679 and @entity17068 . Cultured thymocytes from MyrAkt @entity19 , on the other hand, express high levels of @entity43679 , suggesting that the hypothesized organ size control mechanisms may down-regulate the expression of this molecule. @entity5 cells, similar to MyrAkt thymocytes in culture, express high levels of @entity43679 . These findings support the hypothesis that @entity5 induction is caused by the failure of organ size control mechanisms to down-regulate @entity43679 and to block MyrAkt-promoted G(1) progression.

@entity5 induction by an XXXX -MyrAkt transgene is delayed by mechanisms controlling the size of the thymus.

@entity704 :: ('MESH:D013945', 'Disease') :: ['thymomas'] @entity29939 :: ('16818(Tax:10090)', 'Gene') :: ['Lck'] @entity19 :: ('10090', 'Species') :: ['mice', 'Transgenic mice', 'transgenic mice'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Primary tumor', 'tumors'] @entity11953 :: ('12567(Tax:10090)', 'Gene') :: ['cdk4'] @entity1994 :: ('11651(Tax:10090)', 'Gene') :: ['Akt'] @entity43679 :: ('12445(Tax:10090)', 'Gene') :: ['cyclin D3'] @entity17068 :: ('12566(Tax:10090)', 'Gene') :: ['cdk2']
@entity29939 :: (16818(Tax:10090),Gene) :: ['Lck']
