Home LiteratureArticle Details
PMID: 9990064 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 4 ·1999-02-16 ·Pages 1563-8

Podsypanina K, Ellenson LH, Nemes A, Gu J, Tamura M, Yamada KM, Cordon-Cardo C, Catoretti G, Fisher PE, Parsons R

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.

MeSH Terms
Animals Animals, Newborn Crosses, Genetic Embryonic and Fetal Development Female Gene Expression Regulation, Developmental Genes, Tumor Suppressor Genetic Predisposition to Disease Genotype Hamartoma Syndrome, Multiple/genetics Heterozygote Male Mice Mice, Knockout Neoplasms, Experimental/genetics,pathology PTEN Phosphohydrolase Phosphoric Monoester Hydrolases/biosynthesis,deficiency,genetics Pregnancy Restriction Mapping Tumor Suppressor Proteins
Chemicals
Tumor Suppressor Proteins Phosphoric Monoester Hydrolases PTEN Phosphohydrolase
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Podsypanina 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
Nemes A
Gu J
Tamura M
Yamada K M
Cordon-Cardo C
Catoretti G
Fisher P E
Parsons R
References (40)
40 references, click to expand
  1. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene.
    Science. 1992 May 1;256(5057):668-70 PMID: 1350108
  2. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections.
    J Pathol. 1992 Dec;168(4):357-63 PMID: 1484317
  3. Colorectal polyps in Cowden's disease (multiple hamartoma syndrome).
    Am J Surg Pathol. 1984 Oct;8(10):763-70 PMID: 6496844
  4. Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue.
    Nat Genet. 1995 Oct;11(2):155-63 PMID: 7550343
  5. Targeted mutation in the Fas gene causes hyperplasia in peripheral lymphoid organs and liver.
    Nat Genet. 1995 Nov;11(3):294-300 PMID: 7581453
  6. The Emu-bcl-2 transgene enhances antigen-induced germinal center formation in both BALB/c and SJL mice but causes age-dependent germinal center hyperplasia only in the lymphoma-prone SJL strain.
    Am J Pathol. 1995 Aug;147(2):422-33 PMID: 7639335
  7. CD43 (S7) expression identifies peripheral B cell subsets.
    J Immunol. 1994 Dec 15;153(12):5503-15 PMID: 7989752
  8. Expanding the role of Peyer's patches in B-cell ontogeny.
    Immunol Today. 1996 Jan;17(1):30-9 PMID: 8652050
  9. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.
    Science. 1997 Mar 28;275(5308):1943-7 PMID: 9072974
  10. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers.
    Nat Genet. 1997 Apr;15(4):356-62 PMID: 9090379
  11. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome.
    Nat Genet. 1997 May;16(1):64-7 PMID: 9140396
  12. The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation.
    Nat Genet. 1997 Jun;16(2):161-70 PMID: 9171827
  13. Diffuse esophageal glycogenic acanthosis: an endoscopic marker of Cowden's disease.
    Am J Gastroenterol. 1997 Jun;92(6):1038-40 PMID: 9177527
  14. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta.
    Cancer Res. 1997 Jun 1;57(11):2124-9 PMID: 9187108
  15. Germline mutations in PTEN are present in Bannayan-Zonana syndrome.
    Nat Genet. 1997 Aug;16(4):333-4 PMID: 9241266
  16. Conversion by Peyer's patch lymphocytes of human enterocytes into M cells that transport bacteria.
    Science. 1997 Aug 15;277(5328):949-52 PMID: 9252325
  17. Deletion of PTEN in a patient with Bannayan-Riley-Ruvalcaba syndrome suggests allelism with Cowden disease.
    Am J Med Genet. 1997 Sep 5;71(4):489-93 PMID: 9286463
  18. Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in primary breast carcinomas.
    Cancer Res. 1997 Sep 1;57(17):3657-9 PMID: 9288766
  19. Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma.
    Cancer Res. 1997 Sep 1;57(17):3660-3 PMID: 9288767
  20. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies.
    Cancer Res. 1997 Sep 15;57(18):3935-40 PMID: 9307275
  21. PTEN1 is frequently mutated in primary endometrial carcinomas.
    Nat Genet. 1997 Oct;17(2):143-4 PMID: 9326929
  22. Somatic mutations of PTEN in glioblastoma multiforme.
    Cancer Res. 1997 Oct 1;57(19):4183-6 PMID: 9331071
  23. PTEN gene mutations are seen in high-grade but not in low-grade gliomas.
    Cancer Res. 1997 Oct 1;57(19):4187-90 PMID: 9331072
  24. PTEN/MMAC1 mutations in endometrial cancers.
    Cancer Res. 1997 Nov 1;57(21):4736-8 PMID: 9354433
  25. Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain.
    Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12479-84 PMID: 9356475
  26. Frequent inactivation of PTEN/MMAC1 in primary prostate cancer.
    Cancer Res. 1997 Nov 15;57(22):4997-5000 PMID: 9371490
  27. MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines.
    Cancer Res. 1997 Dec 1;57(23):5221-5 PMID: 9393738
  28. Pten, a candidate tumor suppressor gene, maps to mouse chromosome 19.
    Mamm Genome. 1998 Jan;9(1):88-90 PMID: 9434957
  29. Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.
    Hum Mol Genet. 1998 Mar;7(3):507-15 PMID: 9467011
  30. Homozygous deletion of the PTEN tumor suppressor gene in a subset of prostate adenocarcinomas.
    Clin Cancer Res. 1998 Mar;4(3):811-5 PMID: 9533551
  31. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.
    J Biol Chem. 1998 May 29;273(22):13375-8 PMID: 9593664
  32. Landscaping the cancer terrain.
    Science. 1998 May 15;280(5366):1036-7 PMID: 9616081
  33. Allelic loss of chromosome 10q23 is associated with tumor progression in breast carcinomas.
    Oncogene. 1998 Jul 9;17(1):123-7 PMID: 9671321
  34. Pten is essential for embryonic development and tumour suppression.
    Nat Genet. 1998 Aug;19(4):348-55 PMID: 9697695
  35. Smad3 mutant mice develop metastatic colorectal cancer.
    Cell. 1998 Sep 18;94(6):703-14 PMID: 9753318
  36. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN.
    Cell. 1998 Oct 2;95(1):29-39 PMID: 9778245
  37. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice.
    Curr Biol. 1998 Oct 22;8(21):1169-78 PMID: 9799734
  38. Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC.
    Curr Biol. 1998 Oct 22;8(21):1195-8 PMID: 9799739
  39. The lipid phosphatase activity of PTEN is critical for its tumor supressor function.
    Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13513-8 PMID: 9811831
  40. The PTEN/MMAC1 tumor suppressor induces cell death that is rescued by the AKT/protein kinase B oncogene.
    Cancer Res. 1998 Dec 15;58(24):5667-72 PMID: 9865719
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.4.1563
Published
1999-02-16
Pages
1563-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC15517
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.96.4.1563 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2