title: PRDX1 and PRDX6 are repressed in papillary thyroid carcinomas via BRAF V600E-dependent and -independent mechanisms.
abstract: Many clinical studies highlight the dichotomous role of PRDXs in human cancers, where they can exhibit strong tumor-suppressive or tumor-promoting functions. Recent evidence suggests that lower expression of PRDXs correlates with cancer progression in colorectal cancer (CRC) or in esophageal squamous carcinoma. In the thyroid, increased levels of PRDX1 has been described in follicular adenomas and carcinomas, as well as in thyroiditis, while reduced levels of PRDX6 has been found in follicular adenomas. We studied the expression of PRDX1 and PRDX6, in a series of thyroid tissue samples, covering different thyroid diseases, including 13 papillary thyroid carcinomas (PTCs). Our results show that PRDX1 and PRDX6 are significantly reduced in all PTCs compared to normal tissues, to non-neoplastic tissue (MNG) or follicular neoplasms. This reduction is strongly evident in PTCs harboring BRAF V600E (31% of our cases). Using TPC-1 and BCPAP and FRTL-5 cell lines, we demonstrate for the first time that the presence of BRAF V600E is responsible of the hypoexpression of PRDX1 and PRDX6 both at mRNA and protein levels. Finally, independently of BRAF status, we observe an interesting correlation between the tumor size, the presence of lymph node metastasis and the lowest PRDX1 and PRDX6 levels. Therefore, these data indicate that PRDX1 and PRDX6 expression not only may play a key role in papillary thyroid carcinogenesis via a BRAF V600E-dependent mechanism, but their determination could be considered as potential tumor marker for indicating tumor progression in PTCs, independently of BRAF status.
authors: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors: Arianna
authors: A
authors: Nicolussi
authors: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors: Sonia
authors: S
authors: D'Inzeo
authors: Department of Experimental and Clinical Sciences, 'G. d'Annunzio' University Foundation, Chieti-Pescara, Italy.
authors: Gabriella
authors: G
authors: Mincione
authors: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors: Amelia
authors: A
authors: Buffone
authors: Department of Experimental and Clinical Sciences, 'G. d'Annunzio' University Foundation, Chieti-Pescara, Italy.
authors: Maria Carmela
authors: MC
authors: Di Marcantonio
authors: Department of Experimental and Clinical Sciences, 'G. d'Annunzio' University Foundation, Chieti-Pescara, Italy.
authors: Roberto
authors: R
authors: Cotellese
authors: Department of Experimental and Clinical Sciences, 'G. d'Annunzio' University Foundation, Chieti-Pescara, Italy.
authors: Annadomenica
authors: A
authors: Cichella
authors: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors: Carlo
authors: C
authors: Capalbo
authors: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy.
authors: Cira
authors: C
authors: Di Gioia
authors: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy.
authors: Francesco
authors: F
authors: Nardi
authors: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors: Giuseppe
authors: G
authors: Giannini
authors: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors: Anna
authors: A
authors: Coppa
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D054465:Peroxiredoxin VI / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C515940:PRDX1 protein, human; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf