Enhanced expression of EGF receptor and low frequency of ras mutations in X-ray-induced rat thyroid tumours

• Published in: Virchows Archiv : an international journal of pathology Vol. 435; no. 4; pp. 434 - 441
• Main Authors: Haugen, Dagny R. Faksvåg, Lillehaug, Johan R., Akslen, Lars A.
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.10.1999
• Subjects: Animals; Biological and medical sciences; DNA Mutational Analysis; Endocrinopathies; Female; Genes, ras - radiation effects; Immunohistochemistry; Male; Malignant tumors; Medical sciences; Mutation - radiation effects; Neoplasms, Radiation-Induced - chemistry; Neoplasms, Radiation-Induced - genetics; Rats; Rats, Wistar; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, Epidermal Growth Factor - radiation effects; RNA, Messenger - biosynthesis; Thyroid Neoplasms - chemistry; Thyroid Neoplasms - genetics; Thyroid. Thyroid axis (diseases); X-Rays; Endocrinopathy; Immunohistochemistry; Rat; Thyroid gland; Carcinogenesis; X ray irradiation; Epidermal growth factor; Benign neoplasm; Protooncogene; Cytokine; Rodentia; Thyroid diseases; Malignant tumor; Polymerase chain reaction; Pathology; Vertebrata; Experimental disease; Growth factor receptor; Mammalia; Polypeptide; Animal; C-Onc gene; Mutation; Molecular biology; Growth factor
• ISSN: 0945-6317
• DOI: 10.1007/PL00008191

Radiation is recognized as a carcinogenic factor for the thyroid gland. In this experimental study, oncogene expression was investigated in radiation-induced rat thyroid tumours. Forty 3-month-old Wistar rats received X-ray-irradiation to the neck region; 40 animals were untreated controls. After 14 months, thyroid tumours had developed in 25 of the 29 irradiated animals still alive; 76% of these tumours were considered malignant. No tumours developed in controls. Mutations of codons 12-13 and 59-63 of H-, K- and N-ras were analysed by PCR-SSCP (single-strand conformation polymorphism analysis) and sequencing of DNA from thyroid tissue. SSCP indicated a ras mutation frequency of 8%, but only one K-ras codon 12 (Gly-Cys) mutation was confirmed by sequencing. Protooncogene expression was analysed by mRNA slot blot hybridization analysis and immunohistochemistry. K-ras mRNA expression and EGF receptor mRNA and protein expression were significantly increased in the irradiated animals compared with controls, and in tumours versus nontumour tissue. This study of radiation-induced rat thyroid tumours demonstrates that ras expression may be subject to changes apart from activating mutations. Increased expression of EGF receptor in the tumours parallels the situation in human thyroid cancer.