Minimal effects of dietary restriction on neuroendocrine carcinogenesis in Rb+/- mice

The efficacy of dietary restriction in retarding tumor growth is well established in rodents. However, gene and cell lineage specificity of dietary restriction effects is far less defined. Mice with a single copy of the retinoblastoma susceptibility gene (Rb) develop a well-established syndrome of mouse neuroendocrine neoplasia associated with Rb deficiency. Thus, if DR represses tumor growth in this model, it should be unambiguously attributed to the Rb defect in neuroendocrine cell lineages. To address this possibility, Rb(+/-) mice were entered into a diet restriction study. Surprisingly, 40-50% reductions in dietary intake, relative to an ad libitum group, started on either postnatal day 28 or 42 had little to no effect on either the frequency or growth of pituitary tumors either during the latency period (postnatal day 224) or at the time of their natural death. Consistent with cross-section data, survival of 65 diet restricted Rb(+/-) mice was almost identical to that of 67 Rb(+/-) mice fed ad libitum (AL); median life span was 414 and 436 days for AL and DR groups, respectively. These findings indicate that diet restriction provides no significant benefit in delaying growth and progression of neuroendocrine tumors exhibiting loss of RB function. They also introduce the possibility that RB is required for the tumor-repressive effects of DR.