TGF-beta downregulates PTEN via activation of NF-kappaB in pancreatic cancer cells.

American Journal of Physiology. Gastrointestinal and Liver Physiology
Jimmy Y C ChowJohn M Carethers

Abstract

TGF-beta utilizes receptor-activated SMAD signaling to mediate growth suppression; however, non-SMAD signaling that modulates the TGF-beta response in epithelial cells become apparent when the SMAD signaling is abrogated, a common occurrence in pancreatic cancers. Here, we examined whether TGF-beta utilized NF-kappaB to downregulate PTEN, a gene that is rarely mutated in pancreatic cancers. SMAD4-null BxPc3 and CAPAN-1 pancreatic cancer cells were treated with TGF-beta (10 ng/ml) and lysed, and cellular proteins were analyzed by Western blots using p-IkappaB, p65, and PTEN antibodies. PTEN promoter and NF-kappaB activities were assessed by PTEN-luc and p-NF-luc constructs, respectively. Dominant negative p-IkappaB-alpha-M (NF-kappaB superrepressor) was used to block activation of NF-kappaB. Cell motility was assessed by Boyden chamber migration assay. TGF-beta induced IkappaB-alpha phosphorylation followed by NF-kappaB p65 subunit nuclear translocation and increased NF-kappaB activity. IkappaB-alpha-M blocked TGF-beta-induced NF-kappaB activity, reversed downregulated PTEN promoter activity and PTEN expression, and prevented augmentation of cell motility induced by TGF-beta. SMAD4 restoration, but not knockdown of SMAD2 and/or ...Continue Reading

References

Feb 1, 1977·Journal of the National Cancer Institute·J FoghJ D Loveless
Nov 1, 1996·Science·D J Van AntwerpI M Verma
Oct 6, 1998·Annual Review of Biochemistry·J Massagué
Feb 29, 2000·Cell·A Di Cristofano, P P Pandolfi
May 3, 2000·The Journal of Cell Biology·L ChoyR Derynck
Jun 3, 2000·Annual Review of Immunology·M Karin, Y Ben-Neriah
Mar 10, 2001·Experimental Cell Research·L Simpson, R Parsons
Mar 1, 2002·British Journal of Cancer·M P A EbertP Malfertheiner
May 2, 2002·Cell·Sankar Ghosh, Michael Karin
Jan 20, 2004·Molecular and Cellular Biology·Krishna Murthi VasudevanVivek M Rangnekar
Mar 12, 2004·Cancer Letters·Florian R Greten, Michael Karin
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh
Apr 28, 2005·Virchows Archiv : an International Journal of Pathology·Xavier DolcetXavier Matias-Guiu
Jan 24, 2007·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Feb 2, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jimmy Y C ChowJohn M Carethers
Jan 22, 2013·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal

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Citations

Dec 21, 2010·Oncogene·M M ChaturvediB B Aggarwal
Feb 26, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Srinivas Reddy BoreddySanjay K Srivastava
Mar 19, 2013·Oncogene·J StebbingG Giamas
Apr 17, 2012·Advances in Hematology·Naoko OkumuraSatoru Matsuda
Nov 22, 2014·Respiratory Research·Kimberly D Fischer, Devendra K Agrawal
Dec 4, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiang XiaZhengjun Qiu
Jan 18, 2013·Gastroenterology Research and Practice·Linda S LeeJoao A Paulo
Oct 4, 2014·PloS One·Saima Charni ChaabaneJean-Baptiste Demoulin
Jul 30, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Ignacio MontorfanoFelipe Simon
Sep 18, 2013·Infection and Immunity·M Indriati HoodAlla V Ivanova
Dec 5, 2014·Oncotarget·Lakshmi PrabhuTao Lu
Dec 20, 2018·International Journal of Molecular Sciences·Kartick C PramanikManoj K Pandey
Mar 30, 2019·Mini Reviews in Medicinal Chemistry·Shorooq KhaderRavi P Sahu
Dec 26, 2015·The American Journal of Pathology·Annie LauzierClaire M Dubois
Dec 2, 2021·Journal of Physiology and Biochemistry·Hao-Yuan DengHui-Hua Li

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