Prep1 (pKnox1)-deficiency leads to spontaneous tumor development in mice and accelerates EmuMyc lymphomagenesis: a tumor suppressor role for Prep1.
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.
Longobardi
E
E
Università Vita Salute San Raffaele, via Olgettina 60, Milano 20132, Italy.
Iotti
G
G
Di Rosa
P
P
Mejetta
S
S
Bianchi
F
F
Fernandez-Diaz
L C
LC
Micali
N
N
Nuciforo
P
P
Lenti
E
E
Ponzoni
M
M
Doglioni
C
C
Caniatti
M
M
Di Fiore
P P
PP
Blasi
F
F
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000209:etiology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology
D018398:Homeodomain Proteins; C491412:Pknox1 protein, mouse