Avaliação da expressão das sirtuinas em carcinomas do endométrio

As sirtuinas são enzimas modificadoras das histonas que participam na regulação do metabolismo, divisão celular e envelhecimento. O seu papel na carcinogénese é complexo e está ainda a ser desvendado. Dada a associação dos carcinomas endometriais com factores hormonais, metabólicos e envelhecimento, este trabalho teve como objectivo caracterizar a expressão das sirtuinas nestes tumores. Através da avaliação quantitativa do RNA mensageiro e da expressão proteica, verificou-se que a expressão das sirtuinas, em particular da SIRT1 e SIRT7, está alterada nos carcinomas endometriais quando comparada com o endométrio não neoplásico. Estes achados sugerem que as sirtuinas poderão tem um papel na patogénese dos carcinomas endometriais. Será importante aprofundar este estudo dado que os inibidores das sirtuinas são uma terapêutica anticancerígena promissora.

Autores e Afiliações:
Carla Bartosch ^1,2,3, Sara Monteiro-Reis ^1,2, Diogo Almeida-Rios ^1,2, Renata Vieira ¹, Armando Castro ⁴, Manuel Moutinho ⁴, Marta Rodrigues ^4, Inês Graça ², José Manuel Lopes ^3,4,5,*, Carmen Jerónimo ^2,6,*

¹ Department of Pathology, Portuguese Oncology Institute-Porto (IPO-Porto), Porto, Portugal

² Cancer Epigenetics & Biology Group, Research Center, Portuguese Oncology Institute-Porto, Porto, Portugal

³ Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal

⁴ Department of Pathology, Centro Hospitalar São João (CHSJ), Porto, Portugal

⁵ IPATIMUP (Institute of Molecular Pathology and Immunology, University of Porto), Porto, Portugal

⁶ Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal

* These authors are Joint senior authors

Abstract:
Sirtuins participate in hormone imbalance, metabolism and aging, which are important processes for endometrial cancer (EC) development. Sirtuins mRNA expression (SIRT1 to 7) was determined in 76 ECs (63 Type I, 12 Type II and one mixed EC), and 30 non-neoplastic endometria (NNE) by quantitative real-time PCR. SIRT1 and SIRT7 protein expression was evaluated by immunohistochemistry using Allred score. Compared to NNE, ECs showed SIRT7 (p < 0.001) mRNA overexpression, whereas SIRT1 (p < 0.001), SIRT2 (p < 0.001), SIRT4 (p < 0.001) and SIRT5 (p < 0.001) were underexpressed. No significant differences were observed for SIRT3 and SIRT6. Type II ECs displayed lower SIRT1 (p = 0.032) and SIRT3 (p = 0.016) transcript levels than Type I ECs. Concerning protein expression, SIRT1 immunostaining median score was higher in ECs compared to NNE epithelium (EC = 5 vs. NNE = 2, p < 0.001), while SIRT7 was lower in ECs (EC = 6 vs. NNE = 7, p < 0.001). No significant associations were found between SIRT1/7 immunoexpression and histological subtype, grade, lymphovascular invasion or stage. Our data shows that sirtuins are deregulated in EC. The diversity of expression patterns observed suggests that sirtuins may have distinctive roles in endometrial cancer similarly to what has been described in other cancer models.

Revista: Oncotarget

Link: http://www.ncbi.nlm.nih.gov/pubmed/26701732