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Estrogen receptor variants in normal human mammary tissue
E R Leygue1, P H Watson, L C Murphy
1Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Canada.
Journal of the National Cancer Institute
|March 6, 1996
Summary
Estrogen receptor (ER) variant mRNAs are present in normal breast tissue, but their expression levels are significantly lower compared to breast cancer tissues, suggesting deregulation in cancer.
Area of Science:
- Molecular biology
- Oncology
- Genetics
Background:
- Estrogen receptor (ER) variant mRNAs are found in breast cancer, with levels increasing during tumor progression.
- These variants are speculated to play a role in the transition from hormone-dependent to hormone-independent breast cancer.
Purpose of the Study:
- To determine the presence of ER variant mRNAs in normal human breast tissues.
- To compare the expression levels of ER variants between normal and cancerous breast tissues.
Main Methods:
- Analysis of RNA from normal breast tissues (reduction mammoplasties, adjacent to tumors) and breast tumor specimens.
- Use of reverse transcription and polymerase chain reaction (PCR) to detect various exon-deleted and truncated ER variants.
- Semiquantitative PCR and statistical analysis (Mann-Whitney test) to compare variant expression relative to wild-type ER mRNA.
Main Results:
- Multiple ER variant mRNAs, including truncated and exon-deleted forms, were detected in all normal breast tissue samples.
- The expression of exon 5-deleted ER variant mRNA was significantly lower in normal tissue compared to tumor tissue (P < .001).
- A similar trend of lower expression was observed for exon 7-deleted ER variant mRNA in normal tissue, though not statistically significant (P = .476).
Conclusions:
- Several ER variant mRNAs are indeed present in normal human breast tissue.
- The expression levels of certain ER variants are lower in normal breast tissue than in tumor tissue.
- Mechanisms generating ER variants exist in normal tissue and may be altered in breast cancer, warranting further investigation into their role in cancer development and progression.