Han Q X, Allegretto E A, Shao Z M, Kute T E, Ordonez J, Aisner S C, Rishi A K, Fontana J A
Department of Medicine, University of Maryland Cancer Center, Baltimore, USA.
Diagn Mol Pathol. 1997 Feb;6(1):42-8. doi: 10.1097/00019606-199702000-00007.
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.
维甲酸通过与一系列核受体（即维甲酸受体（RARs）或维甲酸X受体）结合来调节基因活性、细胞生长和分化。维甲酸（RA）对雌激素受体（ER）阳性乳腺癌的抑制作用似乎是通过RARα介导的。雌激素可上调ER阳性乳腺癌细胞系中的RARα。在本研究中，我们使用免疫组织化学和图像细胞术定量分析，检测了ER阳性的MCF7和ER阴性的MDA-MB-231人乳腺癌细胞系以及10例ER阴性和9例ER阳性浸润性导管乳腺癌标本中的RARα表达。MCF7细胞表达的RARα蛋白水平比MDA-MB-231细胞高两倍。通过免疫染色检测并用图像细胞术定量分析发现，这些细胞中的RARα表达被雌二醇上调。ER阳性乳腺癌标本中的RARα水平也比ER阴性标本高约两倍。因此，通过免疫组织化学染色检测和图像细胞术定量分析评估，ER阳性乳腺肿瘤中的RARα表达显著升高。ER阴性肿瘤中RARα蛋白水平的降低以及RA介导的生长抑制作用的丧失是否在ER阴性肿瘤转移潜能增加中起作用，仍有待确定。
