Skip to main content
main-content

01.12.2012 | Short communication | Ausgabe 1/2012 Open Access

Molecular Cancer 1/2012

IRF5 promotes the proliferation of human thyroid cancer cells

Zeitschrift:
Molecular Cancer > Ausgabe 1/2012
Autoren:
Michele Massimino, Paolo Vigneri, Manuela Fallica, Annamaria Fidilio, Alessandra Aloisi, Francesco Frasca, Livia Manzella
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1476-4598-11-21) contains supplementary material, which is available to authorized users.
Michele Massimino, Paolo Vigneri contributed equally to this work.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

MM, MF, AF and AA carried out the research. FF participated in coordination and data analysis. LM and PV designed the study and drafted the manuscript. All authors read and approved the final manuscript.

Abstract

Background

Interferon Regulatory Factor 5 is a transcription factor that regulates the expression of genes involved in the response to viral infection and in the stimulation of the immune system. Moreover, multiple studies have demonstrated that it negatively regulates cell growth and oncogenesis, favoring cell differentiation and apoptosis.
Thyroid carcinoma represents 98% of all thyroid malignancies and has shown a steady increase in incidence in both the USA and western European countries.

Findings

We investigated the expression, localization and function of IRF5 in thyroid cancer cells and found that it is highly expressed in both primary and immortalized thyroid carcinomas but not in normal thyrocytes. IRF5 levels were variably modulated by Interferon alpha but IRF5 only localized in the cytoplasmic compartment, thus failing to induce p21 expression as previously reported in different cell models. Furthermore, ectopic IRF5 increased both the proliferation rate and the clonogenic potential of malignant thyroid cells, protecting them from the cytotoxic effects of DNA-damaging agents. These results were directly attributable to IRF5, as demonstrated by the reduction in colony-forming ability of thyroid cancer cells after IRF5 silencing. An IRF5-dependent induction of endogenous B-Raf observed in all thyroid cancer cells might contribute to these unexpected effects.

Conclusions

These findings suggest that, in thyroid malignancies, IRF5 displays tumor-promoting rather than tumor-suppressor activities.
Zusatzmaterial
Additional file 1 : IRF5 shows cytoplasmic localization in thyroid cancer cells after IFN a treatment. The specified cell lines were treated with 1000 U/mL IFNa for 24 hours. Cells were then labeled for IRF5 using the indicated secondary antibody. Hoechst and phalloidin were employed to stain nuclear and cytoplasmic compartments. (PDF 9 MB)
12943_2011_1022_MOESM1_ESM.pdf
Additional file 2 : IRF5 v3 shows cytoplasmic localization in thyroid cancer cells. The specified cell lines were lentivirally infected with IRF5-GFP v3 and the proteins intracellular localization was analyzed by immunofluorescence. (PDF 4 MB)
12943_2011_1022_MOESM2_ESM.pdf
Additional file 3 : IRF5 tyrosine phosphorylation is not modulated by DNA-damaging agents in thyroid cancer cells. Whole lysates of the specified cell lines treated with 2 μM Doxorubicin (DOXO) or 5 μg/mL cisdiamminedichloroplatinum (CDDP) for the indicated times were subjected to an anti-phosphotyrosine (pY) immunoprecipitaion and subsequently blotted for IRF-5. G immunoglobulines (IgG) were used as a loading control. (PDF 1 MB)
12943_2011_1022_MOESM3_ESM.pdf
Authors’ original file for figure 1
12943_2011_1022_MOESM4_ESM.png
Authors’ original file for figure 2
12943_2011_1022_MOESM5_ESM.pdf
Authors’ original file for figure 3
12943_2011_1022_MOESM6_ESM.pdf
Authors’ original file for figure 4
12943_2011_1022_MOESM7_ESM.png
Authors’ original file for figure 5
12943_2011_1022_MOESM8_ESM.pdf
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2012

Molecular Cancer 1/2012 Zur Ausgabe

Neu im Fachgebiet Onkologie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Onkologie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise