The cDNA sequence of human c-erb-A, the cellular counterpart of the viral oncogene v-erb-A, indicates that the protein encoded by the gene is related to the steroid hormone receptors. Binding studies with the protein show it to be a receptor for thyroid hormones.

The c- erb-A gene encodes a thyroid hormone receptor

Hormone binding and localization of the c-erb-A protein suggest that it is a receptor for thyroid hormone, a nuclear protein that binds to DNA and activates transcription. In contrast, the product of the viral oncogene v-erb-A is defective in binding the hormone but is still located in the nucleus.

The c-erb-A protein is a high-affinity receptor for thyroid hormone

NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3)

Recently the gene for the cellular tumour antigen p53, a phos-phoprotein found in increased concentration in a variety of human cells1, has been mapped to region 17q22 by in situ hybridization techniques and has been shown to translocate to the chromosome carrying the translocation [t(15 ; 17)] associated with acute pro-myelocytic leukaemia (APL)2. Based on this finding it has been postulated that this gene has a role in the pathogenesis of APL2. Here we present evidence that the gene for p53 is not located on the long arm of chromosome 17, but maps to band 17pl3. We therefore suggest that this gene is not directly involved in the chromosome translocation observed in APL.

Localization of gene for human p53 tumour antigen to band 17p13

A complementary DNA clone derived from rat brain messenger RNA has been isolated on the basis of homology to the human thyroid hormone receptor gene. Expression of this complementary DNA produces a high-affinity binding protein for thyroid hormones. Sequence analysis and the mapping of this gene to a distinct human genetic locus indicate the existence of multiple human thyroid hormone receptors. Messenger RNA from this gene is expressed in a tissue-specific fashion with highest levels in the central nervous system.

Identification of a novel thyroid hormone receptor expressed in the mammalian central nervous system

A human cDNA library was screened for sequences homologous to the erbA gene of avian erythroblastosis virus (AEV). One such clone, cHerbA-1, was used to map the chromosomal location of highly homologous human sequences that were found to be present on chromosome 17 as judged by Southern blot screening of a panel of mouse-human hybrid cell lines segregating human chromosomes. cHerbA-1 was hybridized in situ to metaphase chromosomes from a normal male subject and from a female patient with an acute promyelocytic leukemia (APL) having the typical t(15;17) translocation. The results localized the cellular c-erbA sequences on chromosome 17 to the q21-q24 region of normal chromosomes and indicated that the c-erbA sequences remained on the 17q- chromosome in the APL cells, suggesting that they could be assigned to the 17(q21-q22) region. For additional data, we hybridized human neoplastic cells derived from a poorly differentiated acute leukemia carrying a t(17;21) translocation with thymidine kinase (TK)-deficient LMTK- mouse cells. A resulting hybrid, containing only the 21q+ chromosome, did not have human c-erbA sequences. Since the breakpoint on 17q in this translocation was similar to that in the APL t(15;17) translocation, this supported the assignment of c-erbA to the q21-q22 region of chromosome 17. The apparent close proximity of the c-erbA sequences to the chromosomal breakpoints in these two leukemias suggests a possible role for this oncogene homologue in the development of these neoplasms.

G Laws

Papers

A human c-erbA oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia