Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems.
Pten/Mmac1+/- heterozygous mice exhibited neoplasms in multiple organs including the endometrium, liver, prostate, gastrointestinal tract, thyroid, and thymus. Loss of the wild-type allele was detected in neoplasms of the thymus and liver. Surprisingly, tumors of the gastrointestinal epithelium developed in association with gut lymphoid tissue. Tumors of the endometrium, thyroid, prostate, and liver were not associated with lymphoid tissue and appeared to be highly mitotic. In addition, these mice have nonneoplastic hyperplasia of lymph nodes that was caused by an inherited defect in apoptosis detected in B cells and macrophages. Examination of peripheral lymphoid tissue including lymphoid aggregates associated with polyps revealed that the normal organization of B and T cells was disrupted in heterozygous animals. Taken together, these data suggest that PTEN is a regulator of apoptosis and proliferation that behaves as a "landscaper" tumor suppressor in the gut and a "gatekeeper" tumor suppressor in other organs.
Podsypanina
K
K
Departments of Pathology and Medicine, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, P&S 14-453, New York, NY 10032, USA.
Ellenson
L H
LH
Nemes
A
A
Gu
J
J
Tamura
M
M
Yamada
K M
KM
Cordon-Cardo
C
C
Catoretti
G
G
Fisher
P E
PE
Parsons
R
R
D000818:Animals; D000831:Animals, Newborn; D003433:Crosses, Genetic; D005314:Embryonic and Fetal Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics; D006579:Heterozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D011247:Pregnancy; D015183:Restriction Mapping; D025521:Tumor Suppressor Proteins