Nuclear envelope irregularity is induced by RET/PTC during interphase.
Nuclear envelope (NE) irregularity is an important diagnostic feature of cancer, and its molecular basis is not understood. One possible cause is abnormal postmitotic NE re-assembly, such that a rounded contour is never achieved before the next mitosis. Alternatively, dynamic forces could deform the NE during interphase following an otherwise normal postmitotic NE re-assembly. To distinguish these possibilities, normal human thyroid epithelial cells were microinjected with the papillary thyroid carcinoma oncogene (RET/PTC1 short isoform, known to induce NE irregularity), an attenuated version of RET/PTC1 lacking the leucine zipper dimerization domain (RET/PTC1 Deltazip), H (V-12) RAS, and labeled dextran. Cells were fixed at 6 or 18 to 24 hours, stained for lamins and the products of microinjected plasmids, and scored blindly using previously defined criteria for NE irregularity. 6.5% of non-injected thyrocytes showed NE irregularity. Neither dextran nor RAS microinjections increased NE irregularity. In contrast, RET/PTC1 microinjection induced NE irregularity in 27% of cells at 6 hours and 37% of cells at 18 to 24 hours. RET/PTC1 Deltazip induced significantly less irregularity. Since irregularity develops quickly, and since no mitoses and only rare possible postmitotic cells were scored, postmitotic NE re-assembly does not appear necessary for RET/PTC signaling to induce an irregular NE contour.
Fischer
Andrew H
AH
Department of Pathology, Emory University Hospital, Atlanta, Georgia, USA. Fischa01@ummhc.org
Taysavang
Panya
P
Jhiang
Sissy M
SM
D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007399:Interphase / Q000502:physiology*; D008845:Microinjections; D008938:Mitosis / Q000502:physiology; D009685:Nuclear Envelope / Q000187:drug effects* / Q000648:ultrastructure*; D015514:Oncogene Proteins, Fusion / Q000008:administration & dosage / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases; D013961:Thyroid Gland / Q000187:drug effects; D013997:Time Factors
D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human