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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.
Insights
Estrogen receptor (ER) alpha mRNA exon deletions were investigated in breast cancer. The exon 5 deletion variant was more frequent in ER-positive cancers, but does not appear to act as a dominant positive.
Area of Science:
- Molecular biology
- Cancer research
- Genetics
Background:
- Estrogen receptor (ER) alpha mRNA exon deletions are a potential mechanism for ER function loss.
- Understanding ER variants is crucial for breast cancer treatment strategies.
Purpose of the Study:
- To investigate the expression of specific exons (3, 5, and 7) in ER alpha mRNA.
- To determine the frequency of exon deletion variants in human breast cancers and non-cancerous tissues.
Main Methods:
- Reverse transcriptase polymerase chain reaction (RT-PCR) was used to analyze ER alpha mRNA.
- Expression levels of wild-type and deleted exons were quantified in 64 breast cancer tissues and 8 non-cancerous breast tissues.
Main Results:
- Wild-type ER alpha mRNA was detected in all non-cancerous tissues.
- Exon deletions for variants 5 (d5) and 7 (d7) were found in both cancerous and non-cancerous tissues, but exon 3 deletion was not detected.
- The ratio of d5/w5 was significantly higher in ER protein (pER) positive and progesterone receptor protein (pPgR) negative breast cancer cases.
Conclusions:
- The exon 5 deletion variant of ER alpha mRNA was detected in breast cancer tissues.
- The exon 5 deletion does not appear to function as a dominant positive in the context of ER alpha expression.