All-trans-retinoic acid modulates expression levels of thyroglobulin and cytokines in a new human poorly differentiated papillary thyroid carcinoma cell line, KTC-1

• Published in: The journal of clinical endocrinology and metabolism Vol. 85; no. 8; pp. 2889 - 2896
• Main Authors: KUREBAYASHI, J, TANAKA, K, OTSUKI, T, MORIYA, T, KUNISUE, H, UNO, M, SONOO, H
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.08.2000
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Carcinoma, Papillary - genetics; Carcinoma, Papillary - pathology; Carcinoma, Papillary - ultrastructure; Cell Differentiation; Cell Division; Chemotherapy; Cytokines - genetics; DNA-Binding Proteins - genetics; Endocrinopathies; Gene Expression Regulation, Neoplastic - drug effects; Genes, p53; Growth Inhibitors - genetics; Humans; Interleukin-6 - genetics; Leukemia Inhibitory Factor; Lymphokines - genetics; Malignant tumors; Medical sciences; Mice; Mice, Nude; Nuclear Proteins - genetics; Paired Box Transcription Factors; PAX8 Transcription Factor; Pharmacology. Drug treatments; Polymorphism, Single-Stranded Conformational; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Thyroglobulin - genetics; Thyroid Gland - metabolism; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; Thyroid Neoplasms - ultrastructure; Thyroid Nuclear Factor 1; Thyroid. Thyroid axis (diseases); Trans-Activators - genetics; Transcription Factors - genetics; Transcription, Genetic; Transplantation, Heterologous; Tretinoin - pharmacology; Tumor Cells, Cultured; Endocrinopathy; Human; Antineoplastic agent; Immunohistochemistry; Papillary carcinoma; Thyroid diseases; Cytokine; Retinoid; Male; Thyroid gland; Malignant tumor; Gene expression; Genetic determinism; In vitro; Biological activity; Pathology; Thyroglobulin; Adult; Molecular biology; Tretinoin
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.85.8.2889

A new human thyroid carcinoma cell line, KTC-1, was established from the malignant pleural effusion of a recurrent thyroid carcinoma patient. Cytogenetic analysis revealed a normal karyotype, and no p53 mutation in exons 5-9 was detected. This cell line is tumorigenic in athymic nude mice. Histological findings by light and electron microscopy, such as the absence of follicular structures and the existence of intranuclear cytoplasmic inclusions and psammoma bodies, indicated transplanted tumors to be a poorly differentiated papillary thyroid carcinoma. A low expression level of thyroglobulin was detected by immunocytochemistry and RT-PCR. Messenger ribonucleic acid (mRNA) expression of thyroid transcription factor-1 and PAX-8 was also detected. No mRNA expression of TSH receptors, thyroid peroxidase, or Na+/I- symporter was detected. Interleukin-6 and leukemia inhibitory factor were secreted into the medium. These findings suggest this cell line to be functionally poorly differentiated. Moreover, all-trans-retinoic acid increased the mRNA expression of thyroglobulin and decreased both the mRNA expression and secretion of interleukin-6 and leukemia inhibitory factor while significantly stimulating growth. RT-PCR analysis of retinoic acid receptors (RARs) revealed that KTC-1 cells express a moderate level of RARalpha and -gamma, but a low level of RARbeta. This cell line may be useful for studying redifferentiation therapy for thyroid carcinoma.