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Estrogen Receptor Mutants/Variants in Human Breast Cancer.

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Annual rept. 15 Nov 94-14 Nov 95,

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We have identified in a range of human breast cancer biopsy samples, several known and unknown estrogen receptor ER variant niRNAs as well as some ER niRNAs containing inserted nucleotide sequences. The variant ER mRNAs are likely generated by alternative splicing mechanisms, while the inserted ER mRNAs are likely t6 be generated from a mutated ER allele in the tumor cells. All types of variant ER mRNAs so far identified, could be detected in normal human mammary tissue. Interestingly, the expression of some of these variant ER mRNAs was significantly higher in breast tumors than in normal breast tissue. Moreover, the expression of at least one ER mRNA variant relative to the wild-type ER mRNA was significantly increased in breast tumors with characteristics of poor prognosis and lack of sensitivity to endocrine therapies. Our data suggest that the mechanisms generating ER variant mRNAs exist in normal breast tissue and may be deregulated in breast cancer tissues. Further, the data support and are consistent with our working hypothesis that the expression andor altered expression of variantabnormal ER in human breast cancer is one mechanism associated with the development of endocrine resistance and the progression from hormone dependence to independence.

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  • Medicine and Medical Research
  • Biochemistry
  • Anatomy and Physiology

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