ESTABLISHMENT OF ANAPLASTIC THYROID-CARCINOMA CELL-LINES USEFUL FOR ANALYSIS OF CHEMOSENSITIVITY AND CARCINOGENESIS

Anaplastic thyroid carcinoma (ATC) is usually associated with a poor p rognosis, with most patients dying within a few months. The mechanism of its carcinogenesis is unclear, and its rapid growth and spread ofte n prevent effective surgical therapy. Thus, chemotherapy is necessary. However, ATC is often resistant to anticancer drugs. Therefore, predi ction of chemosensitivity is important in selecting appropriate treatm ent. In this study, after the establishment of three cell lines (K119, KOA2, and IAA) from patients with ATC, we analyzed them for abnormali ties in certain oncogenes (myc, ras, ret, and c-erbB2) and the p53 tum or suppressor gene. Only one of three cell lines (KOA2) had a N-ras mu tation [codon 61 CAA(Gln)-->CGA(Arg)] and a p53 gene mutation [exon 6 codon 192 Caa(Gln)-->TAG(stop)]. We also investigated their in vitro d rug sensitivity and compared it with clinical chemosensitivity, retros pectively. In vitro drug sensitivity was determined using an adhesive tumor cell culture system. Only the K119 cells were sensitive to adria mycin and cisplatin in. vitro. The other two were resistant to them in vitro. These results paralleled the clinical responses. We also evalu ated the in vitro drug sensitivity of a poorly differentiated thyroid carcinoma cell line (SMP) and papillary thyroid carcinoma cell lines ( NPA). None of the five cell lines expressed the multidrug resistance g ene (mdr-1). In conclusion, we established ATC cell lines that are sui table models for characterizing the nature of multidrug resistance and carcinogenesis.