Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems

Katrina Podsypanina, Lora Hedrick Ellenson, Adriana Nemes, Jianguo Gu, Masahito Tamura, Kenneth M. Yamada, Carlos Cordon-Cardo, Giorgio Catoretti, Peter E. Fisher, Ramon Parsons

Research output: Contribution to journalArticlepeer-review

849 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1563-1568
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number4
DOIs
StatePublished - 16 Feb 1999
Externally publishedYes

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