Expression of the ErbA-beta class of thyroid hormone receptors is selectively lost in human colon carcinoma.

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Abstract

Members of the erbA gene family are involved both in control of differentiation and in neoplasia. V-erbA, a retroviral oncogene, blocks avian erythroid differentiation. V-erbA-related transcripts are physiologically expressed in multiple normal tissues. They encode a family of transcriptional regulatory factors, some of which are thyroid hormone receptors. In man, two genes, erbA-alpha and erbA-beta, are transcriptionally active. We examined expression of erbA-related transcripts in normal and neoplastic colon. In normal colon mucosa, as well as in a colon polyp and in a colon polyp cell line, three characteristic erbA-related transcripts were consistently found. One transcript of 6 kb was erbA-beta related. Two transcripts of 2.7 and 5.2 kb were erbA-alpha related. In eight patients' colon carcinomas expression of the 6-kb erbA-beta transcript was absent or markedly diminished when compared with the same patients' noninvolved mucosa. In contrast, expression of the two erbA-alpha transcripts was the same in both colon carcinoma and noninvolved mucosa. No evidence was found of erbA-beta gene deletion in any of the tumors lacking erbA-beta expression. These data suggest that selective loss of normally present erbA-beta gene expression accompanies malignant transformation of the colonic epithelial cell.

Authors

S Markowitz, M Haut, T Stellato, C Gerbic, K Molkentin