Bollig-Fischer Aliccia, Thakur Archana, Sun Yuan, Wu Jiusheng, Liao D Joshua
Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA;
Int J Biomed Sci. 2012 Mar;8(1):51-63.
There are many estrogen receptor α (ERα) antibodies available but few of them target a rodent ERα. Using the MC-20 antibody raised against the C-terminus of mouse ERα, we show in this communication that in the mammary gland of female mice and rats, the wild type (wt) ERα was detected on immunoblots as a dominant protein only during lactation, and the protein was lactating specific as it migrated slightly faster than the 67-kD wt ERα in the uterus, likely due to a different phosphorylation status. In contrast, in the nulliparous, pregnant, involuting and involuted mammary glands, the dominant protein recognized by MC-20 was about 61-kD, which is dubbed herein as "MC-20 reactive protein" or MC20RP in abbreviation as its identity is unknown. Our results showed that it was not derived from proteolysis or de-phosphorylation of the 67-kD ERα and was unlikely to be translated from an ERα mRNA variant. Ovariectomy decreased the lactating specific wt ERα but increased the 61-kD MC20RP in the mammary tumors from MMTV-c-myc transgenic mice but these two proteins in the uterus were unaffected. The 61-kD MC20RP was decreased in the mammary tumors, compared with proliferating mammary glands, in estrogen-treated ACI rats. These results suggest that while the lactating specific wt ERα alone or together with the MC20RP may sustain lactation, the MC20RP may support proliferation of the mammary gland and some mammary tumors.
有许多雌激素受体α(ERα)抗体可供使用,但其中针对啮齿动物ERα的抗体很少。在本报告中,我们使用针对小鼠ERα C末端产生的MC-20抗体表明,在雌性小鼠和大鼠的乳腺中,野生型(wt)ERα仅在哺乳期在免疫印迹上被检测为主要蛋白,并且该蛋白具有泌乳特异性,因为它在子宫中迁移速度略快于67-kD wt ERα,这可能是由于不同的磷酸化状态。相比之下,在未生育、怀孕、退化和已退化的乳腺中,MC-20识别的主要蛋白约为61-kD,由于其身份未知,在此被称为“MC-20反应性蛋白”或简称为MC20RP。我们的结果表明,它不是由67-kD ERα的蛋白水解或去磷酸化产生的,也不太可能从ERα mRNA变体翻译而来。卵巢切除术降低了MMTV-c-myc转基因小鼠乳腺肿瘤中泌乳特异性wt ERα的水平,但增加了61-kD MC20RP的水平,而子宫中的这两种蛋白未受影响。在雌激素处理的ACI大鼠中,与增殖性乳腺相比,乳腺肿瘤中的61-kD MC20RP水平降低。这些结果表明,虽然泌乳特异性wt ERα单独或与MC20RP一起可能维持泌乳,但MC20RP可能支持乳腺和一些乳腺肿瘤的增殖。