Beta catenin and cytokine pathway dysregulation in patients with manifestations of the "PTEN hamartoma tumor syndrome"

BMC Medical Genetics

Research Article

Paola Izzo¹  Lorella Paparo¹  Martina Galatola¹  Marina De Rosa¹  Francesca Duraturo¹  Mimmo Turano²  Giovanni Battista Rossi³ 

[1] Dipartimento di Biochimica e Biotecnologie Mediche and CEINGE Biotecnologie Avanzate, Università di Napoli Federico II, via S. Pansini 5, 80131, Naples, Italy;Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, Via Cinthia, 80126, Naples, Italy;Istituto Nazionale dei Tumori - Fondazione G. Pascale, via M. Semmola, 80131, Naples, Italy;

关键词: PTEN hamartoma tumor syndrome;    PTEN;    β-catenin;    TNFα receptors;   

DOI  :  10.1186/1471-2350-13-28

 received in 2011-09-21, accepted in 2012-04-20,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe "PTEN hamartoma tumor syndrome" (PHTS) includes a group of syndromes caused by germline mutations within the tumor suppressor gene "phosphatase and tensin homolog deleted on chromosome ten" (PTEN), characterized by multiple polyps in the gastrointestinal tract and by a highly increased risk of developing malignant tumours in many tissues.The current work clarifies the molecular basis of PHTS in three unrelated Italian patients, and sheds light on molecular pathway disregulation constitutively associated to PTEN alteration.MethodsWe performed a combination of RT-PCR, PCR, sequencing of the amplified fragments, Real Time PCR and western blot techniques.ResultsOur data provide the first evidence of β-catenin accumulation in blood cells of patients with hereditary cancer syndrome caused by germ-line PTEN alteration. In addition, for the first time we show, in all PHTS patients analysed, alterations in the expression of TNFα, its receptors and IL-10. Importantly, the isoform of TNFRI that lacks the DEATH domain (TNFRSF1β) was found to be overexpressed.ConclusionIn light of our findings, we suggest that the PTEN pathway disregulation could determine, in non-neoplastic cells of PHTS patients, cell survival and pro-inflammatory stimulation, mediated by the expression of molecules such as β-catenin, TNFα and TNFα receptors, which could predispose these patients to the development of multiple cancers.

【 授权许可】

Unknown   
© Galatola et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.