Signal transducer and activator of transcription expression 3 (STAT3) in potentially malignant oral lesions
DOI:
https://doi.org/10.5935/2525-5711.20190024Palavras-chave:
STAT3 Protein, Leukoplakia, ImmunohistochemistryResumo
Objective: The present study evaluated the expression and activation of the STAT-3 in potentially malignant disorders and its association with dysplasia grade. Methods: Twenty-four fragments from two distinct areas, namely the buccal mucosa and the tongue, with 10 cases of hyperkeratosis without dysplasia and 14 cases of hyperkeratosis with mild, moderate or severe dysplasia, were analyzed. Immunohistochemistry for STAT-3 and P-STAT-3 was performed using the biotin-streptavidin-peroxidase method. Results: In both hyperkeratosis with and without dysplasia STAT-3 demonstrated cytoplasmic ex- pression in epithelial layers. Nuclear expression in hyperkeratosis with mild or moderate dysplasia was seen. In hyperkeratosis with severe dysplasia the lower epithelial layers there were areas exhibiting loss of labeling. P-STAT-3 showed nuclear expression in all epithelial layers, except for the superficial layer, in hyperkeratosis without dysplasia. In hyperkeratosis with mild and moderate dysplasia, nuclear expression was seen in all epithelial layers, except for the superficial layer, with a few cells showing no expression. Conclusion: Regarding hyperkeratosis with severe dysplasia, there was loss of expression in a higher number of cells. In both hyperkeratosis with and without dysplasia, STAT-3 activation was found to be abnormal and no significant difference for STAT-3 expression at different dysplasia grades was observed.
Referências
Warnakulasuriya S. Lack of molecular markers to predict malignant potential of oral precancer. J Pathol. 2000; 190:427-22.
El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. WHO Classification of Head and Neck Tumours. WHO/IARC Classification of Tumours, , 2017; 4th Edition, V.9
Darnell Jr JE, Kerr JM, Stark GR. Jak-STAT pathways and transcriptional activation in response to IFNs and other ex- tracellular signaling proteins. Science 1994; 264:1415-1421.
Mali SB. Review of STAT3 (Signal Transducers and Activators of Transcription) in head and neck cancer. Oral Oncology 2015; 51: 565–569.
Siveen KS, Sikka S, Surana R, Dai, X., Zhang, J., Kumar, A. P., et al. Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors. Biochim Biophys Acta 2014; 1845:136–54.
Buettner R, Mora LB, Jove R. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res 2002; 8: 945-5
Shinagawa K, Yanamoto S, Naruse T, T., Kawakita, A., Morishita, K., SakamotoClinical Roles of Interleukin-6 and STAT3 in Oral Squamous Cell Carcinoma. Pathol Oncol Res 2017; 23:425–431.
Cury PR, Furuse C, de Araújo NS, de Araújo VC. Signal transducer and activator of transcription-3 expression and activation is deregulated in actinic cheilitis. Journal Cutaneus Pathology 2007; 34: 606–611.
Quadros MRD, Peruzzi F, Kari C, Rodeck U. Complex regulation of signal transducers and activators of transcription 3 activation in normal and malignant keratinocytes. Cancer Res. 2004; 64:3934-3939
Nagpal J, Mishra R, Das BR. Activation of Stat-3 as one of the early events in tobacco chewing-mediated oral carcinogenesis. Cancer 2002; 94:2393-2400
Page C, Huang M, Jin X, K Cho J Lilja R K Reynolds, et al. Elevated phosphorylation of AKT and Stat3 in prostate, breast, and cervical cancer cells. Int J Oncol 2000; 17:23.
de Araújo VC, Furuse C, Cury PR, Altemani A, de Araújo NS. STAT3 expression in salivary gland tumours. Oral Oncology 2008; 44:439-45
Silver DL, Naora H, Liu J, Cheng W, Montell DJ. Activated signal transducer and activator of transcription (STAT) 3: localization in focal adhesions and function in ovarian cancer cell motility. Cancer Res 2004; 64:3550-3558
Shah NG, Trivedi TI, Tankshali RA, Shah NG, Trivedi TI, Tankshali RA., Goswami JA., Jetly DH, Kobawala TP. Stat3 expression in oral squamous cell carcinoma: association with clinicopathological parameters and survival. Int J Biol Markers 2006; 21:175-83.
Pectasides E, Egloff AM, Sasaki C, Kountourakis P, Burtness B, Fountzilas G, et al. Nuclear localization of signal transducer and activator of transcription 3 in head and neck squamous cell carcinoma is associated with a better prognosis. Clin Cancer Res 2010; 16:2427–34.
Johnston PA, Grandis JR. STAT3 signaling: anticancer strategies and challenges. Mol Interv 2011; 11:18-26.
Bowman T, S Sebti, W Dalton, R Jover. Signal transducers and activators of transcription: novel targets for anticancer therapeutics. Cancer Control 2000; 6:427-435
Bromberg J. Stat proteins and oncogenesis. J Clin Invest 2002; 109:1139-1142.
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Copyright (c) 1969 Maria Carolina de Lima Jacy Monteiro, Renata Tucci, Juliana Costa de Oliveira, Amy Louise Brown, Ney Soares de Araújo, Vera Cavalcanti de Araújo, Cristiane Furuse
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.