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 receptors (RARs) or retinoid X receptors. Retinoic acid (RA) inhibition of estrogen receptor (ER)-positive breast carcinoma seems to be mediated through RAR alpha. Estrogens upregulate RAR alpha in ER-positive breast carcinoma cell lines. In this study we examined RAR alpha expression in the ER-positive MCF7 and ER-negative MDA-MB-231 human breast carcinoma cell lines as well as in 10 ER-negative and 9 ER-positive infiltrating ductal breast carcinoma specimens using immunohistochemistry and quantitation by image cytometry. MCF7 cells expressed twofold higher levels 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 two-fold higher RAR alpha levels than their ER-negative counterparts. Thus, RAR alpha expression is significantly elevated in ER-positive breast tumors as assessed by detection and quantitation using immunohistochemical staining and image cytometry, 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 remains to be determined.
Han
Q X
QX
Department of Medicine, University of Maryland Cancer Center, Baltimore, USA.
Allegretto
E A
EA
Shao
Z M
ZM
Kute
T E
TE
Ordonez
J
J
Aisner
S C
SC
Rishi
A K
AK
Fontana
J A
JA
D001943:Breast Neoplasms / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D019044:Image Cytometry; D007150:Immunohistochemistry; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis*; D000072482:Retinoic Acid Receptor alpha; D014407:Tumor Cells, Cultured
C000607071:RARA protein, human; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha