Prep1 (pKnox1)-deficiency leads to spontaneous tumor development in mice and accelerates EmuMyc lymphomagenesis: a tumor suppressor role for Prep1.

Molecular Oncology
Elena LongobardiFrancesco Blasi

Abstract

The Prep1 homeodomain transcription factor is essential for embryonic development. 25% of hypomorphic Prep1(i/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) Prep1(i/i) cells into lethally irradiated mice induces lymphomas. In agreement with the above data, haploinsufficiency of a different Prep1-deficient (null) allele accelerates EmuMyc 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.

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Citations

Nov 16, 2017·Scientific Reports·Giorgia MaroniDmitry Penkov
Mar 23, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Francesco BlasiLeila Dardaei
Jan 18, 2017·Scientific Reports·Chiara ZucchelliChiara Bruckmann
Mar 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·Leila DardaeiFrancesco Blasi
Aug 27, 2014·Proceedings of the National Academy of Sciences of the United States of America·Maurizio RisolinoPasquale Verde
Jul 28, 2019·International Journal of Molecular Sciences·Giorgia MaroniMaria Cristina Magli
Aug 17, 2019·Development·Dorothea Schulte, Dirk Geerts
Feb 6, 2013·Biochemistry. Biokhimii︠a︡·D N PenkovV A Tkachuk
Oct 17, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ilaria CimminoFrancesco Oriente
Mar 27, 2021·Frontiers in Cell and Developmental Biology·Marina ReichlmeirDorothea Schulte
Sep 10, 2010·Development·Luis C Fernandez-DiazFrancesco Blasi
May 6, 2021·International Journal of Molecular Sciences·Lina-Marie BriuJean-Charles Cadoret

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