title: Elevated expression of retinoic acid receptor-alpha (RAR alpha) in estrogen-receptor-positive breast carcinomas as detected by immunohistochemistry.
abstract: 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.
authors.affiliation: Department of Medicine, University of Maryland Cancer Center, Baltimore, USA.
authors.forename: Q X
authors.initials: QX
authors.lastname: Han
authors.forename: E A
authors.initials: EA
authors.lastname: Allegretto
authors.forename: Z M
authors.initials: ZM
authors.lastname: Shao
authors.forename: T E
authors.initials: TE
authors.lastname: Kute
authors.forename: J
authors.initials: J
authors.lastname: Ordonez
authors.forename: S C
authors.initials: SC
authors.lastname: Aisner
authors.forename: A K
authors.initials: AK
authors.lastname: Rishi
authors.forename: J A
authors.initials: JA
authors.lastname: Fontana
mesh_terms: 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
chemical_list: C000607071:RARA protein, human; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha