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Estrogen Receptor Variant Messenger RNA Lacking Exon 4 in Estrogen-responsive Human Breast Cancer Cell Lines¹

Istituto Nazionale per la Ricerca sul Cancro, Laboratory of Molecular Biology, I-16132 Genova [U. P., E. F., G. V.], and Hormone Biochemistry Laboratories, Palermo University Medical School, Cancer Hospital Centre "M. Ascoli," Experimental Oncology Unit, Palermo Branch, Palermo [E. F., L. C.], Italy

We have identified a messenger RNA coding for a variant estrogen receptor jointly expressed with the normal mRNA in the estrogen receptor-positive, -responsive mammary carcinoma cell lines MCF-7 and ZR 75-1 by means of reverse transcription polymerase chain reaction. This variant mRNA was not observed in estrogen receptor-negative, -unresponsive MDA-MB 231 cells. Partial sequence analysis of the variant complementary DNA revealed identity to sequences of the estrogen receptor exons 3, 5, and 6, but the absence of the entire exon 4. We suggest that this variant receptor messenger is created by alternative splicing. The variant protein is expected to lack most of the hinge domain and part of the hormone binding domain, and it might have a cellular distribution and estrogen-binding affinity different from that of the normal receptor protein.

¹ Supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC), the Consiglio Nazionale delle Ricerche (CNR), and the Ministero della Sanità to (G. V.). L. C. was supported by a grant from the AIRC and CNR, Special Project Aging. E. F. holds an AIRC Fellowship.

² To whom reprint requests should be addressed, at Istituto Nazionale per la Ricerca sul Cancro, Laboratory of Molecular Biology, Viale Benedetto XV, 10, I-16132 Genova, Italy.

Received 12/14/92. Accepted 12/31/92.

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