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Variant Human Breast Tumor Estrogen Receptor with Constitutive Transcriptional Activity¹

University of Texas Health Science Center, Department of Medical Oncology, San Antonio, Texas 78284-7884 [S. A. W. F., S. D. F., G. C. C., A. K. T., W. L. M.], and Baylor College of Medicine, Houston, Texas 77030 [D. P. M., Z. N., B. W. O.]

Since progesterone receptor (PgR) is normally induced by estrogen, breast cancers lacking estrogen receptor (ER) would also be expected to lack PgR. However, a small percentage of breast cancers are ER- yet PgR+. These tumors might possess an ER which is defective in estrogen binding but is still functional in stimulating estrogen-responsive genes such as PgR. We have now detected such a variant, lacking exon 5 of the hormone-binding domain, using complementary DNA amplified by the polymerase chain reaction. This variant was the predominate ER RNA expressed in three ER-/PgR+ tumors. Furthermore, the variant ER constitutively activates transcription of a normally estrogen-dependent gene construct in yeast cells. The variant ER could explain the expression of PgR in certain tumors and have therapeutic implications.

¹ Supported by an American Cancer Society Institutional Grant and NIH grant CA52351-01 to S. A. W. F. and NIH Grant CA30195 to W. L. M., who is a Clinical Research Professor of the American Cancer Society.

² To whom requests for reprints should be addressed, at Department of Medicine/Oncology, University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78284-7884.

Received 7/ 9/90. Accepted 9/25/90.

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