Activin A and activin receptors in thyroid cancer.
Proliferation is controlled by a network of mitogenic and growth inhibitory factors. Transforming growth factor-beta1 (TGF-beta1) and activin A are the most important growth inhibitors of benign follicular epithelial cells of the human thyroid. The effects of these substances on malignant primary thyrocytes are not known. We have examined the growth regulatory effects of activin A and TGF-beta1 in primary cultures derived from four papillary cancers, two follicular thyroid cancers, and three benign thyroid tissues. Malignant cells demonstrated resistance to activin and TGF-beta1 or reversal to a weak but significant mitogenic effect (p < 0.001). We also evaluated 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 subtypes of type I and type II activin receptors were demonstrated. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) demonstrated a significant threefold downregulation of alk4-1 receptors in papillary (n = 25) and follicular (n = 18) thyroid cancers as compared to normal thyroids (n = 12) (p < 0.001). To our knowledge these are the first data to demonstrate reversal of activin and TGF-beta1 effects in thyroid malignancy and to demonstrate changes of the type Ib activin receptor expression in thyroid malignancy.
Department of General Surgery and Trauma Surgery, Heinrich-Heine-University, Düsseldorf, Germany. SchulteKM@med.uni-duesseldorf.de
K M
KM
Schulte
C
C
Jonas
R
R
Krebs
H D
HD
Röher
D029404:Activin Receptors; D028341:Activins; D018263:Adenocarcinoma, Follicular / Q000737:chemistry / Q000473:pathology; D000368:Aged; D017398:Alternative Splicing; D017209:Apoptosis; D002291:Carcinoma, Papillary / Q000737:chemistry / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002648:Child; D003470:Culture Media; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D017978:Receptors, Growth Factor / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003470:Culture Media; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D029404:Activin Receptors