Influence of RET/PTC1 and RET/PTC3 oncoproteins in radiation-induced papillary thyroid carcinomas on amounts of cytoskeletal protein species.
Radiation-induced human papillary thyroid carcinomas (PTCs) show a high prevalence of fusions of the RET proto-oncogene to heterologous genes H4 (RET/PTC1) and ELE1 (RET/PTC3), respectively. In contrast to the normal membrane-bound RET protein, aberrant RET fusion proteins are constitutively active oncogenic cytosolic proteins that can lead to malignant transformation of thyroid epithelia. To detect specific tumor-associated protein changes that reflect the effect of RET/PTC fusion proteins, we analyzed normal thyroid tissues, thyroid tumors of the RET/PTC1 and RET/PTC3 type and their respective lymph node metastases by a combination of high-resolution two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-mass spectrometry. PTCs without RET rearrangements served as controls. Several cytoskeletal protein species showed quantitative changes in tumors and lymph node metastases harboring RET/PTC1 or RET/PTC3. We observed prominent C-terminal actin fragments assumedly generated by protease cleavages induced due to enhanced amounts of the active actin-binding protein cofilin-1. In addition, three truncated vimentin species, one of which was proven to be headless, were shown to be highly abundant in tumors and metastases of both RET/PTC types. The observed protein changes are closely connected with the constitutive activation of RET-rearranged oncoproteins and reflect the importance to elucidate disease-related typical signatures on the protein species level.
Zeindl-Eberhart
Evelyn
E
Institute of Pathology, Ludwig-Maximilians-University of Munich, Thalkirchner Strasse 36, 80337, Munich, Germany. Evelyn.ZeindlEberhart@med.uni-muenchen.de
Liebmann
Sibylle
S
Jungblut
Peter Roman
PR
Mattow
Jens
J
Schmid
Monika
M
Kerler
Rosi
R
Rabes
Hartmut Manfred
HM
D000293:Adolescent; D002277:Carcinoma; D002291:Carcinoma, Papillary; D002648:Child; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D011995:Recombination, Genetic; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D057825:Two-Dimensional Difference Gel Electrophoresis; D055815:Young Adult
D003598:Cytoskeletal Proteins; C000715470:MAS1 protein, human; D015514:Oncogene Proteins, Fusion; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human