AMP-activated protein kinase signaling is upregulated in papillary thyroid cancer

• Published in: European journal of endocrinology Vol. 169; no. 4; pp. 521 - 528
• Main Authors: Vidal, Ana Paula, Andrade, Bruno M, Vaisman, Fernanda, Cazarin, Juliana, Pinto, Luis Felipe Ribeiro, Breitenbach, Marisa Maria Dreyer, Corbo, Rossana, Caroli-Bottino, Adriana, Soares, Fernando, Vaisman, Mario, Carvalho, Denise P
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01.10.2013
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; AMP-Activated Protein Kinases - metabolism; Biological and medical sciences; Carcinoma - metabolism; Carcinoma - pathology; Carcinoma, Papillary; Clinical Study; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Humans; Immunohistochemistry - methods; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Phosphorylation - physiology; Retrospective Studies; Signal Transduction - physiology; Thyroid Cancer, Papillary; Thyroid Gland - metabolism; Thyroid Gland - pathology; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; Tumors; Up-Regulation - physiology; Vertebrates: endocrinology; Young Adult; Papillary carcinoma; Enzyme; Transferases; Non-specific serine/threonine protein kinase; Malignant tumor; cAMP-dependent protein kinase; Endocrinology; Cancer
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/EJE-13-0284

AMP-activated protein kinase (AMPK) is activated by the depletion in cellular energy levels and allows adaptive changes in cell metabolism and cell survival. Recently, our group described that AMPK plays an important role in the regulation of iodide and glucose uptake in thyroid cells. However, AMPK signaling pathway in human thyroid carcinomas has not been investigated so far.ObjectiveTo evaluate the expression and activity of AMPK in papillary thyroid carcinomas.MethodsWe examined total and phosphorylated AMPK (tAMPK and pAMPK) and phosphorylated acetyl-CoA-carboxylase (pACC) expressions through imunohistochemistry, using a tissue microarray block composed of 73 papillary thyroid carcinomas (PAP CA) or microcarcinomas (PAP MCA) and six adenoma (AD) samples from patients followed at the Federal University Hospital. The expression levels were compared with the non-neoplastic tissues from the same patient. Two different pathologists analyzed the samples and attributed scores of staining intensity and the proportion of stained cells. A total index was obtained by multiplying the values of intensity and the proportion of stained cells (INTxPROP).ResultstAMPK, pAMPK, and pACC showed a predominant cytoplasmic staining in papillary carcinomas, adenomas, and non-neoplastic thyroid tissues. However, the intensity and the proportion of stained cells were higher in carcinomas, so that a significant increase was found in the INTxPROP score both in PAP CA and PAP MCA, when compared with their respective controls.ConclusionOur results show unequivocally that AMPK pathway is highly activated in papillary thyroid carcinomas; however, more studies are necessary to understand the pathophysiological significance of AMPK activation in thyroid carcinogenesis.