Expression of Estrogen Receptor Alpha Exon 5 and 7 Deletion Variant in Human Breast Cancers

Background: An exon deletion variant of estrogen receptor (ER) mRNA has been reported, as one of the possible mechanisms of loss of ER function.

Methods: We examined the expression of exons 3, 5, and 7 in ER alpha mRNA and the frequency of exon deletion variant expression in 64 cases of human breast cancers and in 8 non-cancerous breast tissues using reverse transcriptase polymerase chain reaction (RT-PCR).

Results: Approximately the same amount of wild-type (wt) mRNA was detected in all the non-cancerous breast tissues. In cancers, expression of wild-type exon 3 (w3), exon 5 (w5), and exon 7 (w7) was detected in 93.5%, 93.5%, and 91.3% of ER alpha protein (pER) positive cases, respectively, and 27.8%, 38.9%, and 44.4% in negative cases, respectively (p < 0.0001, p = 0.0035, and p = 0.0002). Although the variants for exon 5 (d5) and 7 (d7) were detected in both non-cancerous and cancerous tissues respectively, the variant for exon 3 was not detected at all. Comparatively, the ratio of d5/w5 was significantly higher in pER positive and progesterone receptor protein (pPgR) negative cases.

Conclusions: We suspect that the exon 5 deletion does not work as a dominant positive.