ELEVATED EXPRESSION OF RETINOIC ACID RECEPTOR-ALPHA (RAR-ALPHA) IN ESTROGEN-RECEPTOR-POSITIVE BREAST CARCINOMAS AS DETECTED BY IMMUNOHISTOCHEMISTRY

Retinoids modulate gene activity, cell growth, and differentiation by binding to a series of nuclear receptors, i.e., retinoic acid receptor s (RARs) or retinoid X receptors. Retinoic acid (RA) inhibition of est rogen receptor (ER)-positive breast carcinoma seems to be mediated thr ough RAR alpha. Estrogens upregulate RAR alpha in ER-positive breast c arcinoma cell lines. In this study we examined RAR alpha expression in the ER-positive MCF7 and ER-negative MDA-MB-231 human breast carcinom a cell lines as well as in 10 ER-negative and 9 ER-positive infiltrati ng ductal breast carcinoma specimens using immunohistochemistry and qu antitation by image cytometry. MCF7 cells expressed twofold higher lev els of RAR alpha protein than MDA-MB-231 cells. RAR alpha expression, as detected by immunostaining and quantitated by image cytometry, was upregulated in these cells by estradiol. ER-positive breast carcinoma specimens also exhibited approximately twofold higher RAR alpha levels than their ER-negative counterparts. Thus, RAR alpha expression is si gnificantly elevated in ER-positive breast tumors as assessed by detec tion and quantitation using immunohisotchemical staining and image cyt ometry, respectively. Whether the decrease in RAR alpha protein levels and loss of RA-mediated growth inhibition in ER-negative tumor plays a role in the increased metastatic potential of ER-negative tumors rem ains to be determined.