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

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.

journal_name

Mol Oncol

journal_title

Molecular oncology

authors

Longobardi E,Iotti G,Di Rosa P,Mejetta S,Bianchi F,Fernandez-Diaz LC,Micali N,Nuciforo P,Lenti E,Ponzoni M,Doglioni C,Caniatti M,Di Fiore PP,Blasi F

doi

10.1016/j.molonc.2010.01.001

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

126-34

issue

2

eissn

1574-7891

issn

1878-0261

pii

S1574-7891(10)00002-5

journal_volume

4

pub_type

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