Morphoproteomics demonstrates activation of mTOR pathway in anaplastic thyroid carcinoma: a preliminary observation.
The mammalian target of rapamycin (mTOR) signaling pathway was studied using immunohistochemical stains on paraffin-embedded tumor tissue from two patients with anaplastic thyroid carcinoma (ATC) and on paraffin-embedded normal thyroid tissue from 23 control patients. Immunoreactivities of p-mTOR, p-Akt, p-p70S6K, and PLD1 were observed in both of the ATCs, with nuclear translocation of p-mTOR, p-Akt, and p-p70S6K. Increased expression of Ki-67, Skp2, and cyclin D1, decreased expression of p27(kip1), and increased mitotic index (MI) were noted in the ATCs in comparison with those of normal thyroid tissue. The results provide evidence of (a) constitutive activation of the mTOR pathway, (b) mTORC2 activation, suggested by the nuclear translocation of p-mTOR, and (c) enhanced cell cycle progression in ATCs. These preliminary findings warrant future studies in a large series of patients with ATC to evaluate a possible molecular basis for treating chemoradioresistant ATC.
Liu
Jing
J
Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston Medical School, Houston, Texas, USA. jing.liu.1@uth.tmc.edu
Brown
Robert E
RE
D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008938:Mitosis; D010739:Phospholipase D / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D040901:Proteomics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions; D058570:TOR Serine-Threonine Kinases; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology
C530104:CCND1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D044786:S-Phase Kinase-Associated Proteins; D019938:Cyclin D1; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D010739:Phospholipase D; C106801:phospholipase D1