Induction of expression of MHC-class-II antigen on human thyroid carcinoma by wild-type p53

Zeki, Kazuya; Tanaka, Yoshiya; Morimoto, Isao; Nishimura, Yasuharu; Kimura, Akinori; Yamashita, Uki; Eto, Sumiya

doi:10.1002/(sici)1097-0215(19980130)75:3<391::aid-ijc11>3.0.co;2-c

Cited by 16 publications

(5 citation statements)

References 17 publications

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“…It has been proposed that functional p53 protein is involved in the induction of antitumor CD4+ cytotoxic-T-cell activity against carcinoma cells [33]. In addition, p53 peptides may be processed and presented to host immune cells by a variety of mechanisms [34, 35].…”

Section: Discussionmentioning

confidence: 99%

P53 and Expression of Immunological Markers May Identify Early Stage Thyroid Tumors

Marcello

Morari

Cunha

et al. 2013

Clinical and Developmental Immunology

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Background. Besides its major role in cell proliferation, DNA repair, and apoptosis, functional p53 protein is involved in the induction of antitumor cytotoxic-T-cell activity against carcinoma cells. We aimed to investigate p53 and immune cell markers utility as diagnostic and prognostic markers of differentiated thyroid cancer (DTC). Methods. ACIS-III system was used to evaluate p53 and immune cell markers including tumor-associated macrophages (TAM); CD68 and tumor-infiltrating lymphocytes (TIL) subsets such as CD3, CD4, CD8, and CD20 in 206 thyroid carcinomas, 105 benign nodules, and 18 normal tissues. Also, TP53 was sequenced in 78 out of 164 patients with papillary thyroid carcinoma. Results. P53 expression was observed more frequently in malignant than in benign lesions (P < 0.0001) and helped discriminate follicular patterned lesions. In addition, p53 was more frequent in smaller (P = 0.0015), unique tumors (P = 0.0286), with thyroiditis (P = 0.0486) and without metastasis at diagnosis (P = 0.0201). TAM was more frequent in P53 negative tumors (P = 0.002). Infiltration of CD8+ TIL was found in 61.7% of P53 positive and 25.6% of P53 negative DTC (P < 0.001). Conclusions. We suggest that p53 and CD8+ TIL immune profile analysis might be useful in DTC.

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Section: Discussionmentioning

confidence: 99%

P53 and Expression of Immunological Markers May Identify Early Stage Thyroid Tumors

Marcello

Morari

Cunha

et al. 2013

Clinical and Developmental Immunology

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“…6,[12][13][14][15][16][17][18] We attempted here a gene therapy approach in which TP53-mediated tumor cell differentiation was combined with the delivery of suicide and cytokine genes under the control of TG enhancer.…”

Section: Discussionmentioning

confidence: 99%

Modulation of retrovirally driven therapeutic genes by mutant TP53 in anaplastic thyroid carcinoma

et al. 2005

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We previously demonstrated that restoration of TP53 activity in anaplastic thyroid carcinoma inhibits cell growth and induces expression of thyroid differentiation markers. Here, we investigated whether TP53 status may condition the expression of therapeutic genes driven by retroviral LTR or tissue-specific enhancer elements. The TP53-defective ARO anaplastic thyroid carcinoma cells were transfected with TP53Val135 , which exhibits wild-type activity at 321C, and transduced with retroviral vectors, in which therapeutic genes were driven either by wild-type LTR or by a reshuffled LTR containing thyroglobulin (TG) enhancer. Both at 37 and 321C, expression of transgenes driven by TG enhancer was 10-fold lower than that obtained with wild-type LTR retroviral vector. TP53 Val135 transfer into ARO cells repressed transcription from wild-type LTR but increased expression of TGdriven therapeutic genes. This effect was markedly enhanced by cell culture at 321C and by TSH treatment. Cytotoxic effects shown after ganciclovir treatment paralleled therapeutic gene expression levels. In conclusion, TP53 status in the tumor cell can influence expression of therapeutic genes. When using retroviral-vector-based gene therapy, wild-type LTR vectors should be employed to target TP53-defective tumors, whereas thyroid-specific promoters should be used for transcriptional targeting of thyroid carcinomas carrying wild-type TP53.

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“…We first verified the efficacy of``gene -inactivation strategy'' with p53-regulated Cre/ loxP system using AxCAyLLZL, Axyp53RECre, and AxCAyCre ( Fig 1 ) in a pair of isogenic cell lines that differs only in their p53 28 ] and normal human thyroid cells with wt -p53. AxCAyLLZL was infected alone or in combination with Axyp53RECre or AxCAyCre into thyroid cells, and LacZ expression levels were assessed by x-gal staining and -galactosidase assay ( Fig 2A and B ).…”

Section: Resultsmentioning

confidence: 99%

“…FRO cells stably expressing wt-p53 (FRO -p53 ) has previously been established. 28 Thyroid tissue samples were obtained by subtotal thyroidectomy from patients with Graves' disease, and normal human thyroid follicular cells in primary culture were prepared as previously described 29 and maintained in Ham's F12 medium with 5% FBS and antibiotics. Informed consent was obtained from each patient.…”

Section: Cells Usedmentioning

confidence: 99%

Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre/loxP system

et al. 2001

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In this article, we evaluated the feasibility of the restricted replication -competent adenoviruses for treatment of anaplastic thyroid carcinomas ( ATCs ) , which are very aggressive and difficult to treat. Because ATCs very often harbor p53 mutations, we used wt -p53 as a regulatory factor to restrict virus replication and cytopathic effect to p53 -mutated cells. The recently reported``gene inactivation strategy'' using p53 -regulated Cre / loxP system was employed; this system consists of two recombinant adenoviruses. One has an expression unit of the synthetic p53 -responsive promoter and the Cre recombinase gene ( Axyp53RECre ) , and another contains two expression units; the first consists of E1A gene flanked by a pair of loxP sites downstream of the constitutive CAG promoter and the second E1B19K gene under the control of the CMV promoter ( AdCALE1AL ) . We expected that coinfection of these two adenoviruses into the cells with wt -p53 would lead to expression of the Cre, which excises E1A gene and switches off E1A expression resulting in no virus replication, whereas in the cells with mutant p53 E1A could be expressed that leads to virus replication and cell lysis. Our in vitro data demonstrate that although infection of AdCALE1AL alone led to E1A expression, viral replication and cytolysis in all the thyroid cells examined irrespective of their p53 status, the double infection did so in FRO cells ( p53 -null ATC ) but not in FRO cells stably expressing wt -p53 and normal thyroid cells with wt -p53. These data indicate that our double infection method may have a potential for treatment of ATC and probably also other p53 -defective cancer cells. Cancer Gene Therapy ( 2001 ) 8, 36 ± 44

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Induction of expression of MHC-class-II antigen on human thyroid carcinoma by wild-type p53

Cited by 16 publications

References 17 publications

P53 and Expression of Immunological Markers May Identify Early Stage Thyroid Tumors

P53 and Expression of Immunological Markers May Identify Early Stage Thyroid Tumors

Modulation of retrovirally driven therapeutic genes by mutant TP53 in anaplastic thyroid carcinoma

Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre/loxP system

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