Beta catenin and cytokine pathway dysregulation in patients with manifestations of the

BMC Medical Genetics

Marina De Rosa³  Paola Izzo³  Giovanni Battista Rossi²  Mimmo Turano¹  Francesca Duraturo³  Lorella Paparo³  Martina Galatola³ 

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

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

Others  :  1177877
DOI  :  10.1186/1471-2350-13-28

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

【 摘 要 】

Background

The "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.

Methods

We performed a combination of RT-PCR, PCR, sequencing of the amplified fragments, Real Time PCR and western blot techniques.

Results

Our 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.

Conclusion

In 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】

   
2012 Galatola et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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