Early cellular abnormalities induced by RET/PTC1 oncogene in thyroid-targeted transgenic mice.
The RET/PTC1 oncogene, a rearranged form of the RET proto-oncogene, has been reported to be associated with human papillary thyroid carcinomas. We have shown that targeted expression of RET/PTC1 in the thyroid gland leads to the development of thyroid carcinomas in transgenic mice with histologic and cytologic similarities to human papillary thyroid carcinoma. To further investigate how RET/PTC1 expression contributes to the pathogenesis of papillary thyroid tumor, the time of tumor onset and the early phenotypic consequences of RET/PTC1 expression in thyrocytes were determined. All high copy transgenic mice developed bilateral thyroid tumors as early as 4 days of age. At embryological days 16-18, increased proliferation rate, distorted thyroid follicle formation and reduced radioiodide concentrating activity were identified in transgenic embryos. The reduced radioiodide concentrating activity was attributed to decreased expression of the sodium-iodide symporter. Our study showed that RET/PTC1 not only increased proliferation of thyrocytes, it also altered morphogenesis and differentiation. These findings provide a model for the role of RET/PTC1 in the formation of abnormal follicles with reduced iodide uptake ability observed in human papillary thyroid carcinoma.
Cho
J Y
JY
Department of Physiology, The Ohio State University, Columbus 43210, USA.
Sagartz
J E
JE
Capen
C C
CC
Mazzaferri
E L
EL
Jhiang
S M
SM
D017668:Age of Onset; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002455:Cell Division; D003409:Congenital Hypothyroidism; D004247:DNA / Q000096:biosynthesis; D018450:Disease Progression; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D009857:Oncogenes; D010641:Phenotype; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D027981:Symporters; D013961:Thyroid Gland / Q000187:drug effects / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000196:embryology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013972:Thyrotropin / Q000494:pharmacology; D013974:Thyroxine / Q000494:pharmacology; D000099209:Sodium-Iodide Symporters
D002352:Carrier Proteins; D004247:DNA; D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D027981:Symporters; D013972:Thyrotropin; D013974:Thyroxine; D000099209:Sodium-Iodide Symporters; C000715470:MAS1 protein, human; C093573:ret-PTC fusion oncoproteins, human