Nuclear envelope organization in papillary thyroid carcinoma.
Papillary thyroid carcinomas (PTCs) have characteristic nuclear shape changes compared to follicular-type thyroid epithelium. We tested the hypothesis that the altered nuclear shape results from altered distribution or expression of the major structural proteins of the nuclear envelope. Lamin A, lamin B1, lamin C, lamin B receptor (LBR), lamina-associated polypeptide 2 (LAP2), emerin, and nuclear pores were examined. PTC's with typical nuclear features by H&E were compared to non-neoplastic thyroid and follicular neoplasms using confocal microscopy, and semi-quantitative immunoblotting. Lamin A/C, lamin B1, LAP2, emerin, and nuclear pores all extend throughout the grooves and intranuclear inclusions of PTC. Their distribution and fluorescent intensity is not predictably altered relative to nuclear envelope irregularities. By immunoblotting, the abundance (per cell) and electrophoretic mobilities of lamin A, lamin B1, lamin C, emerin, and LAP2 proteins do not distinguish PTC, normal thyroid, or follicular neoplasms. These results do not support previously published predictions that lamin A/C expression is related to a loss of proliferative activity. At least three LAP2 isoforms are identified in normal and neoplastic thyroid. LBR is sparse or undetectable in all the thyroid samples. The results suggest that the irregular nuclear shape of PTC is not determined by these nuclear envelope structural proteins per se. We review the structure of the nuclear envelope, the major factors that determine nuclear shape, and the possible functional consequences of its alteration in PTC.
Fischer
A H
AH
Department of Pathology, Emory University Hospital, Atlanta, USA.
Taysavang
P
P
Weber
C J
CJ
Wilson
K L
KL
D015153:Blotting, Western; D018265:Carcinoma, Papillary, Follicular / Q000648:ultrastructure*; D002458:Cell Fractionation; D002499:Centrifugation, Density Gradient; D004586:Electrophoresis; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007536:Isomerism; D007797:Laminin / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D018613:Microscopy, Confocal; D009685:Nuclear Envelope / Q000648:ultrastructure*; D009687:Nuclear Proteins / Q000378:metabolism / Q000648:ultrastructure; D013946:Thymopoietins / Q000276:immunology / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000648:ultrastructure*; D016707:Tissue Fixation
D007797:Laminin; D008565:Membrane Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin