Role of Estrogen Receptor Variants in Tumorgenesis of Human Breast Cancer

Abstract

Abstract : In order to determine whether differences exist in expression of estrogen receptor (ER) variant mRNAs between normal and tumor breast tissues, we have analyzed by reverse transcription-polymerase chain reaction (RT-PCR) ER variants mRNA expression in matched normal breast tissue and breast tumor components from 18 different patients. A higher expression of exon 5-deleted, and of clone 4 ER variants in the tumor component compared to the normal counterpart of matched samples was seen. A general trend toward a higher expression of exon 3-deleted ER variant in the normal tissue was also observed. This is consistent with previous observations made on independent samples. We have described the presence within normal breast as well as in breast tumor tissues of several variant forms of ER-beta mRNA deleted in exon 5, exon 6 and in exon 5+6 sequences. The biological significance of the presence of these variants and of wild-type ER-beta in breast tissue, in particular their role in estrogen/antiestrogen action, remains to be determined. We showed that a significantly (p<0.02) higher ER-alpha/ER-beta ratio was observed in the breast tumors compared with their matched normal breats tissues and that this increase was attributed to a significant (p<0.05) increase in ER-alpha mRNA expression and a lower ER-beta mRNA expression in the tumor compared with that of the normal component in some ER+ cases. Our results suggest that the role of ER-alpha and ER-beta driven pathways and/or their interaction change during breast tumorigenesis.