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mRNA in Tamoxifen-resistant Breast Cancer Patients1
Department of Medicine [V. S., D. S. W., S. L. A.] and Academic Surgical Unit [C. M., M. J. K.], University of Hull, Hull HU6 7RX, England, United Kingdom
Tamoxifen is currently the first-line therapy for treatment of hormone-dependent breast cancer. However, despite initial benefits, most patients eventually relapse. Two groups of patients were identified: (a) a tamoxifen-sensitive group (n = 8); and (b) a tamoxifen-resistant group (n = 9). Using reverse transcription-PCR, the relative expression of mRNA for both estrogen receptor (ER) 
and transforming growth factor 1 was determined in each patient group and quantified against a known reference standard. ER- mRNA was significantly up-regulated in the tamoxifen-resistant group as compared with the tamoxifen-sensitive group (P = 0.001 by Fisher’s exact test), and, consistent with previous findings, transforming growth factor 1 was also up-regulated in the tamoxifen-resistant cohort (P = 0.02). The importance of ER- in tamoxifen resistance was validated using tamoxifen-sensitive and -resistant cell lines, in which it was demonstrated that ER- mRNA was significantly up-regulated in the resistant cells. These results lend further support to a role for ER- as a poor prognostic factor in breast cancer.
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