Papillary thyroid carcinoma oncogene (RET/PTC) alters the nuclear envelope and chromatin structure.
Current evidence suggests the papillary thyroid carcinoma oncogene (RET/PTC) generates papillary thyroid carcinomas in one genetic step. We tested a resulting prediction that RET/PTC expression in thyroid epithelium should be sufficient to cause the changes in nuclear morphology diagnostic of this tumor. Primary cultures of human thyroid epithelial cells were infected with a RET/PTC retroviral construct. Morphological scoring by two independent cytopathologists shows RET/PTC expression by immunohistochemistry to be highly associated (p << 0.0001) with an irregular nuclear contour and a euchromatic appearance compared with non-expressing cells in the same cultures. The altered nuclear morphology is not due to gene transfer or transformation per se as primary thyroid cell cultures infected with a retroviral H-RAS construct differ from RET/PTC-infected cells by showing round nuclear envelopes and coarser chromatin, as determined by the independent scoring of two cytopathologists (p << 0.0001). In addition, RET/ PTC-transfected cells appear to disperse, whereas RAS-transfected cells grow as discrete colonies. The results provide additional support for the hypothesis that RET/PTC is sufficient to cause papillary thyroid carcinomas. A signaling pathway downstream of RET/ PTC leads to restructuring of the nuclear envelope and chromatin, and the signal does not depend entirely, if at all, on a RAS pathway.
Fischer
A H
AH
Department of Pathology, Emory University Hospital, Atlanta, Georgia 30322, USA. afische@emory.edu
Bond
J A
JA
Taysavang
P
P
Battles
O E
OE
Wynford-Thomas
D
D
D016475:3T3 Cells; D000818:Animals; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002843:Chromatin / Q000473:pathology*; D029721:Drosophila Proteins; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D009685:Nuclear Envelope / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012190:Retroviridae; D013961:Thyroid Gland / Q000166:cytology / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D002843:Chromatin; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse