Nuclear PTEN deficiency and heterozygous PTEN loss have distinct impacts on brain and lymph node size.

Defects in PTEN, a critical tumor suppressor, are associated with tumorigenesis and aberrant organ sizes. It has been shown that heterozygous PTEN loss increases brains and neuron size, while the specific loss of nuclear PTEN has the opposite effect. Here, we investigate the impact of a combination of heterozygous PTEN loss and nuclear PTEN loss on the size of various organs, including the brain, liver, thymus, spleen, and inguinal lymph node. We found that the effect of the combination varies among organs. Notably, the combination of heterozygous PTEN loss and nuclear PTEN loss restored the normal size of brains and neurons. In contrast, the liver's size was unaffected by either single PTEN defects or their combination. Strikingly, the size of the inguinal lymph node was greatly increased due to lymphoma by the combination of the two PTEN defects. These data suggest that nuclear PTEN and non-nuclear PTEN function in an antagonistic manner in the brain while acting synergistically in the inguinal lymph node.