{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:29:34Z","timestamp":1772137774219,"version":"3.50.1"},"reference-count":56,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,10,25]]},"abstract":"<jats:p>The inositol phosphatases phosphatase and tensin homologue (PTEN) and Src homology 2 domain\u2013containing inositol phosphatase (SHIP) negatively regulate phosphatidylinositol-3-kinase (PI3K)\u2013mediated growth, survival, and proliferation of hematopoietic cells. Although deletion of PTEN in mouse T cells results in lethal T cell lymphomas, we find that animals lacking PTEN or SHIP in B cells show no evidence of malignancy. However, concomitant deletion of PTEN and SHIP (bPTEN\/SHIP\u2212\/\u2212) results in spontaneous and lethal mature B cell neoplasms consistent with marginal zone lymphoma or, less frequently, follicular or centroblastic lymphoma. bPTEN\/SHIP\u2212\/\u2212 B cells exhibit enhanced survival and express more MCL1 and less Bim. These cells also express low amounts of p27kip1 and high amounts of cyclin D3 and thus appear poised to undergo proliferative expansion. Unlike normal B cells, bPTEN\/SHIP\u2212\/\u2212 B cells proliferate to the prosurvival factor B cell activating factor (BAFF). Interestingly, although BAFF availability may promote lymphoma progression, we demonstrate that BAFF is not required for the expansion of transferred bPTEN\/SHIP\u2212\/\u2212 B cells. This study reveals that PTEN and SHIP act cooperatively to suppress B cell lymphoma and provides the first direct evidence that SHIP is a tumor suppressor. As such, assessment of both PTEN and SHIP function are relevant to understanding the etiology of human B cell malignancies that exhibit augmented activation of the PI3K pathway.<\/jats:p>","DOI":"10.1084\/jem.20091962","type":"journal-article","created":{"date-parts":[[2010,10,18]],"date-time":"2010-10-18T23:34:01Z","timestamp":1287444841000},"page":"2407-2420","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":76,"title":["Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases"],"prefix":"10.1084","volume":"207","author":[{"given":"Ana V.","family":"Miletic","sequence":"first","affiliation":[{"name":"Program of Inflammatory Disease Research, Infectious and Inflammatory Disease Center, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037 1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy N.","family":"Anzelon-Mills","sequence":"additional","affiliation":[{"name":"Program of Inflammatory Disease Research, Infectious and Inflammatory Disease Center, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037 1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Mills","sequence":"additional","affiliation":[{"name":"Program of Inflammatory Disease Research, Infectious and Inflammatory Disease Center, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037 1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidne A.","family":"Omori","sequence":"additional","affiliation":[{"name":"Program of Inflammatory Disease Research, Infectious and Inflammatory Disease Center, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037 1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene M.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Section of Molecular Biology, Division of Biological Sciences 2 , and 3"},{"name":"University of California San Diego Cancer Center, University of California San Diego, La Jolla, CA 92093 2 , and 3"},{"name":"Section of Molecular Biology, Division of Biological Sciences 2 , and 3"},{"name":"University of California San Diego Cancer Center, University of California San Diego, La Jolla, CA 92093 2 , and 3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Mi","family":"Shin","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology 4 and 5"},{"name":"Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852 4 and 5"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey V.","family":"Ravetch","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065 6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Bolland","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology 4 and 5"},{"name":"Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852 4 and 5"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Herbert C.","family":"Morse","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology 4 and 5"},{"name":"Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852 4 and 5"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert C.","family":"Rickert","sequence":"additional","affiliation":[{"name":"Program of Inflammatory Disease Research, Infectious and Inflammatory Disease Center, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037 1"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2010,10,18]]},"reference":[{"key":"2023072521542571900_bib1","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1038\/sj.leu.2404873","article-title":"PIK3CA mutations are mutually exclusive with PTEN loss in diffuse large B-cell lymphoma","volume":"21","author":"Abubaker","year":"2007","journal-title":"Leukemia."},{"key":"2023072521542571900_bib2","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/35000501","article-title":"Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling","volume":"403","author":"Alizadeh","year":"2000","journal-title":"Nature."},{"key":"2023072521542571900_bib3","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/ni892","article-title":"Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function","volume":"4","author":"Anzelon","year":"2003","journal-title":"Nat. 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