title: Involvement of tumor suppressors PTEN and p53 in the formation of multiple subtypes of liposarcoma.
abstract: Liposarcoma (LPS) is a type of soft tissue sarcoma that mostly occurs in adults, and in humans is characterized by amplifications of MDM2 and CDK4. The molecular pathogenesis of this malignancy is still poorly understood and, therefore, we developed a mouse model with conditional inactivation of PTEN and p53 to investigate these pathways in the progression of the disease. We show that deletion of these two tumor suppressors cooperate in the formation of multiple subtypes of LPS (from well-differentiated LPS to pleomorphic LPS). In addition, progression of the tumors is further characterized by the expression of D cyclins and CDK4/6, which allow for continued cell division. Microarray analysis also revealed novel genes that are differentially expressed between different subtypes of LPS, which could aid in understanding the disease and to unravel potential new therapeutic targets.
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Puzio-Kuter
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
authors.forename: S V
authors.initials: SV
authors.lastname: Laddha
authors.affiliation: Icahn School of Medicine at Mount Sinai, Mount Sinai School of Medicine, New York, USA.
authors.forename: M
authors.initials: M
authors.lastname: Castillo-Martin
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Icahn School of Medicine at Mount Sinai, Mount Sinai School of Medicine, New York, USA.
authors.forename: C
authors.initials: C
authors.lastname: Cordon-Cardo
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.|Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Jersey, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Chan
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.|Institute for Advanced Study, Princeton, New Jersey, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Levine
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000378:metabolism; D005260:Female; D008080:Liposarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D051059:PTEN Phosphohydrolase
references.citation: Cancer Genet Cytogenet. 1997 Nov;99(1):14-8
references.pmid: 9352790
references.citation: Genesis. 2002 Feb;32(2):148-9
references.pmid: 11857804
references.citation: Hum Mol Genet. 1999 Aug;8(8):1461-72
references.pmid: 10400993
references.citation: N Engl J Med. 1997 Mar 6;336(10):734
references.pmid: 9045054
references.citation: Cancer Res. 2001 Jun 1;61(11):4569-75
references.pmid: 11389092
references.citation: Nat Genet. 2001 Dec;29(4):418-25
references.pmid: 11694875
references.citation: Nature. 2012 Mar 29;483(7391):598-602
references.pmid: 22388813
references.citation: Clin Cancer Res. 2012 Aug 15;18(16):4325-33
references.pmid: 22733537
references.citation: Cell Death Differ. 2012 Aug;19(8):1381-9
references.pmid: 22388350
references.citation: Genes Dev. 2010 Aug 1;24(15):1580-9
references.pmid: 20679392
references.citation: Genes Dev. 2014 Dec 1;28(23):2613-20
references.pmid: 25452272
references.citation: Virchows Arch. 2010 Mar;456(3):277-85
references.pmid: 20039060
references.citation: Nat Struct Mol Biol. 2012 May;19(5):478-84, S1
references.pmid: 22466965
references.citation: Stem Cells. 2011 Feb;29(2):179-92
references.pmid: 21732477
references.citation: Nat Rev Mol Cell Biol. 2011 Nov;12(11):722-34
references.pmid: 21952300
references.citation: Cell Stem Cell. 2012 Aug 3;11(2):179-94
references.pmid: 22862944
references.citation: Ann Intern Med. 1969 Oct;71(4):747-52
references.pmid: 5360287
references.citation: Genes Chromosomes Cancer. 2011 Nov;50(11):896-907
references.pmid: 21910158
references.citation: Genes Chromosomes Cancer. 1995 Sep;14(1):8-14
references.pmid: 8527390
references.citation: Am J Transl Res. 2013 Apr 19;5(3):359-67
references.pmid: 23634246
references.citation: J Biol Chem. 2007 Jun 29;282(26):19052-61
references.pmid: 17412698
references.citation: Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16386-91
references.pmid: 21930930
references.citation: Genes Chromosomes Cancer. 1999 Jan;24(1):30-41
references.pmid: 9892106
references.citation: Cancer Res. 2007 Jul 15;67(14):6626-36
references.pmid: 17638873
references.citation: Clin Cancer Res. 2014 May 15;20(10):2651-62
references.pmid: 24599933
references.citation: Oncogene. 2014 Jul 3;33(27):3550-60
references.pmid: 23955083
references.citation: Apoptosis. 2013 May;18(5):578-88
references.pmid: 23479126
references.citation: J Cancer Res Clin Oncol. 1998;124(10):532-40
references.pmid: 9829856
references.citation: EMBO J. 2010 Aug 4;29(15):2538-52
references.pmid: 20588255
references.citation: J Pathol. 1997 Jan;181(1):14-24
references.pmid: 9071998
references.citation: Eur J Cancer. 2005 Dec;41(18):2853-60
references.pmid: 16289617
references.citation: BMC Cancer. 2014;14:468
references.pmid: 24965044
references.citation: Lancet Oncol. 2012 Nov;13(11):1133-40
references.pmid: 23084521
references.citation: Sarcoma. 2011;2011:483154
references.pmid: 21253554
references.citation: Am J Pathol. 2008 Apr;172(4):1069-80
references.pmid: 18310505
references.citation: Nat Med. 2007 Jun;13(6):748-53
references.pmid: 17496901
references.citation: Mol Cell Biol. 2003 Sep;23(17):6139-49
references.pmid: 12917336
references.citation: Am J Pathol. 2013 Apr;182(4):1400-11
references.pmid: 23416162
references.citation: Cancer Metab. 2013 Feb 04;1(1):9
references.pmid: 24280180