Enhancement of c-erbA proto-oncogene expression by glucocorticoid hormones in S49.1 lymphoma cells

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190 To our knowledge, this is the first report on the modulation of the c-erbA proto-oncogene expression by a steroid hormone. Multiple forms of c-erbA cDNA have been isolated from several tissues and species [9,10,12-14]. a and forms are to some extent different on the basi~ of nucleic aci~ :Ccluences, although they are largely cross.hybridizing. Furthermore two c-erbAa (a-1 and a-2) cDNAs have been described corresponding to a 6.0 kb and a 2.6 kb mRNA species, respectively, each derived by alternative splicing [15,16]. The size of the c-erbA mRNA observed in our hormone-treated $49.1 cells is 2.6 kb, suggesting that it might correspond to the c.erbAa-2 cDNA previously described [15,16]. This is further suggested by the fact that c-erbAfl mRNA is 6.0 kb long in most of the tissues studied [27]. The c.erbA-encoded proteins have been reported to correspond to the thyroid hormone (T3) receptor [q,!0]. T3 receptors have been observed in normal and leukemic lymphoid cells [28]. Furthermore, thyroid hormone affects in several ways T and B lymphocyte functions (for review Ref. 29). At present time we do not know whether the 2.6 kb RNA increased by dexamethasone treatment in $49.1 cells corresponds to the T3 receptor. In fact, the protein encoded by the 2.6 kb RNA is usually not able to bind T3 [15]. Furthermore, T3 receptor levels correlate with the 6.0 kb c-erbA mRNA species rather than with the 2.6 kb one [27]. The molecular heterogeneity of the c-erbA gene products is paralleled by their heterogeneous biological activity. In fact, differences in the transcriptional regulatory activity and/or the hormone-dependency of the c-erbAa and ,8 subtypes have been described [16-18]. Different functions for v-erbA- and c-erbA-encoded proteins have also been described [9,19,20]. Since v-erbA oncogene-encod~ protein has been shown to affect proliferation and differentiation events leading to cell transformation, it is possible that c-erbA.encoded proteins could mimic and/or antagonize v-erbA in controlling cell functions. In conclusion, we have observed that glucocorticoid hormones are able to control c-erbA proto-oncogene expression in $49.1 lymphoma cells. The functions of c-erbA-encoded proteins in normal and neoplastic lymphoid cells are not known. However, the modulation of c-erbA by a steroid hormone which so dramatically affects lymphocyte functions makes it possible that c-erbA plays an important role in such cell functions and/or in mediating hormone effects~ The association of the modulation of c-erbA gene e:~pression with modifications of cell proliferation and c-myc proto-ot~cogene mRNA levels, suggests that such proto-oncogenes might be involved in the dex~methasone-mediated controi of the proliferation of $49.1 fells. We thank Drs. R.M. Evans and S. Martinotti for providing the c-erbAfl eDNA probe (plasmid pheA4)

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