Prep1 (pKnox1)‐deficiency leads to spontaneous tumor development in mice and accelerates EμMyc lymphomagenesis: A tumor suppressor role for Prep1

摘要

The Prep1 homeodomain transcription factor is essential for embryonic development. 25% of hypomorphic Prep1i/i embryos, expressing the gene at 2% of the normal levels, survive pregnancy and live a normal‐length life. Later in life, however, these mice develop spontaneous pre‐tumoral lesions or solid tumors (lymphomas and carcinomas). In addition, transplantation of E14.5 fetal liver (FL) Prep1i/i cells into lethally irradiated mice induces lymphomas. In agreement with the above data, haploinsufficiency of a different Prep1‐deficient (null) allele accelerates EμMyc lymphoma growth. Therefore Prep1 has a tumor suppressor function in mice.Immunohistochemistry on tissue micrroarrays (TMA) generated from three distinct human cohorts comprising a total of some 1000 human tumors revealed that 70% of the tumors express no or extremely low levels of Prep1, unlike normal tissues. Our data in mice are thus potentially relevant to human cancer.