Activin A and activin receptors in thyroid cancer

Proliferation is controlled by a network of mitogenic and growth inhibitory factors. Transforming growth factor-beta (1) (TGF-beta (1)) and activin A are the most important growth inhibitors of benign follicular epithelial ce lls of the human thyroid. The effects of these substances on malignant prim ary thyrocytes are not known. We have examined the growth regulatory effect s of activin A and TGF-beta (1) in primary cultures derived from four papil lary cancers, two follicular thyroid cancers, and three benign thyroid tiss ues. Malignant cells demonstrated resistance to activin and TGF-beta (1) or reversal to a weak but significant mitogenic effect (p < 0.001). We also e valuated the activin receptor transcription pattern. Isoforms alk4-1, 4-2, and 4-3 were found in benign (n = 12) and malignant (n = 22) tissues. Two s ubtypes of type I and type II activin receptors were demonstrated. Semiquan titative reverse transcription-polymerase chain reaction (RT-PCR) demonstra ted a significant threefold downregulation of alk4-1 receptors in papillary (n = 25) and follicular (n = 18) thyroid cancers as compared to normal thy roids (n = 12) (p <0.001). To our knowledge these are the first data to dem onstrate reversal of activin and TGF-beta (1) effects in thyroid malignancy and to demonstrate changes of the type Ib activin receptor expression in t hyroid malignancy.