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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 8 2889-2896
Copyright © 2000 by The Endocrine Society


Original Studies

All-Trans-Retinoic Acid Modulates Expression Levels of Thyroglobulin and Cytokines in a New Human Poorly Differentiated Papillary Thyroid Carcinoma Cell Line, KTC-11

Junichi Kurebayashi, Katsuhiro Tanaka, Takemi Otsuki, Takuya Moriya, Hironori Kunisue, Masako Uno and Hiroshi Sonoo

Departments of Breast and Thyroid Surgery (J.K., K.T., H.K., H.S.), Hygiene (T.O.), and Radiation Oncology (M.U.), Kawasaki Medical School, Kurashiki, Okayama 701-0192; and Department of Pathology, Tohoku University School of Medicine (T.M.), Sendai, Miyagi 980-8574, Japan

Address all correspondence and requests for reprints to: Junichi Kurebayashi, M.D., Department of Breast and Thyroid Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. E-mail: kure{at}med.kawasaki-m.ac.jp

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 RAR{alpha} and -{gamma}, but a low level of RARß. This cell line may be useful for studying redifferentiation therapy for thyroid carcinoma.




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