THE C-ERBA-BETA THYROID-HORMONE RECEPTOR - EXPRESSION AND CDNA SEQUENCE-ANALYSIS OF THE HORMONE-BINDING DOMAIN IN HUMAN CANCER CELL-LINES

The human c-erbA beta protooncogene encodes a thyroid hormone receptor (comprising a hormone-binding domain and a DNA-binding domain) which modulates expression of specific genes, such as cell differentiation g enes. Using the reverse transcription and polymerase chain reaction (R T-PCR) assay, significant expression of the c-erbA beta gene was detec ted in the SiHa, CaSki, HeLa cervical carcinoma; Hep3B, PLC/PRF/5, Mah lavu hepatocellular carcinoma; HT-1080 fibrosarcoma cell lines; as wel l as in normal MRC-5 embryo lung and FS-4 foreskin fibroblast cell lin es. However, the Molt-4 leukaemia and Raji Burkitt's lymphoma cell lin es exhibited very low levels of c-erbA beta expression. Single-strand conformation polymorphism analysis and direct sequencing of PCR produc ts of the c-erbA beta hormone-binding domain cDNAs of these cell lines revealed identical sequences, but differed from the published human p lacental c-erbA beta sequence by five single base disparities. Sequenc ing of an aberrant fragment fortuitously amplified from the HT-1080 cD NA library demonstrated concordance with the cDNA of pregnancy-specifi c glycoprotein 4, which is related to the tumour marker, carcinoembryo nic antigen.