To study the growth control of human thyroid cells in different stages of differentiation, we established two human thyroid cell lines of adenomatous goiter and papillary carcinoma. A 59-year-old female patient with adenomatous goiter was operated in September 1991, and a 27-year-old female patient with papillary carcinoma in May 1990. The thyroid cell lines were established by successive passage without cellular or genetic manipulations such as fusing other cell lines or oncogenic viral infection. These cell lines, human adenomatous goiter cells (hAG) and human papillary thyroid carcinoma cells (hPTC), exhibited a flattened polygonal shape and proliferated as a monolayer in cell culture. The doubling time of the hAG cells was 60 h in Ham's F12 medium supplemented with 10% fetal bovine serum, and that of the hPTC cells, 18 h in the same medium. Both cell lines expressed mRNA for TSH receptor and secreted cAMP into the medium during incubation with thyrotropin (TSH) at concentrations as low as 0.01 mU/mL. The effects of activators of protein kinase A (PKA), protein kinase C (PKC), tyrosine kinase (TK), and estradiol (E2) on proliferation of the hAG cells and the hPTC cells were assessed by measuring cellular DNA content in 24-well plates with diaminobenzoic acid. TSH stimulated proliferation of the hAG cells, but it inhibited proliferation of the hPTC cells. Since TSH activates two signaling pathways, the adenyl cyclase-PKA system and phospholipase C-PKC system, we tested effects of dibutylyl cAMP (dBC) and phorbol myristate 13-acetate (PMA), separately. dBC stimulated proliferation of the hAG cells, but it inhibited that of the hPTC cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of apoptosis by adenovirus E1A in rodent cells is stimulated by wild type (wt) p53 but completely suppressed by mutated p53. The suppression is overcome by coexpression with Id proteins (Ids). The cells expressing E1A and Ids undergo apoptosis after accumulation in S phase, suggesting that S phase events are perturbed by E1A and Ids. The E1A domains required for induction of apoptosis, analysed by transfection with expression vectors for E1A, Ids and their mutants, followed by¯ow cytometry, reside in Nterminal (positions 17 ± 38), CR1 and CR2 regions. Interaction of E1A with Ids requires the N-terminal and CR1 regions. The cyclin D1 promoter activity in S phase was reduced severely by E1A and this reduction is caused through CR1 and CR2 regions required for interaction with pRB. Analysis of DNA synthesis in G 2 /M arrested cells indicated that E1A is capable of inducing 44 N cells and this E1A-mediated DNA rereplication is enhanced by coexpression with Id-1H. The E1A domains required for induction of DNA rereplication coincide with those required for apoptosis.