Department of Clinical Molecular Biology, EpiGen, Institute of Clinical Medicine, Akershus University Hospital, University of Oslo, Lørenskog, Norway.
BMC Cancer. 2010 Dec 16;10:686. doi: 10.1186/1471-2407-10-686.
Polycomb Group (PcG) proteins are epigenetic silencers involved in maintaining cellular identity, and their deregulation can result in cancer. Expression of Mel-18 and Bmi-1 has been studied in tumor tissue, but not in adjacent non-cancerous breast epithelium. Our study compares the expression of the two genes in normal breast epithelium of cancer patients and relates it to the level of expression in the corresponding tumors as well as in breast epithelium of healthy women.
A total of 79 tumors, of which 71 malignant tumors of the breast, 6 fibroadenomas, and 2 DCIS were studied and compared to the reduction mammoplastic specimens of 11 healthy women. In addition there was available adjacent cancer free tissue for 23 of the malignant tumors. The tissue samples were stored in RNAlater, RNA was isolated to create expression microarray profile. These two genes were then studied more closely first on mRNA transcription level by microarrays (Agilent 44 K) and quantitative RT-PCR (TaqMan) and then on protein expression level using immunohistochemistry.
Bmi-1 mRNA is significantly up-regulated in adjacent normal breast tissue in breast cancer patients compared to normal breast tissue from noncancerous patients. Conversely, mRNA transcription level of Mel-18 is lower in normal breast from patients operated for breast cancer compared to breast tissue from mammoplasty. When protein expression of these two genes was evaluated, we observed that most of the epithelial cells were positive for Bmi-1 in both groups of tissue samples, although the expression intensity was stronger in normal tissue from cancer patients compared to mammoplasty tissue samples. Protein expression of Mel-18 showed inversely stronger intensity in tissue samples from mammoplasty compared to normal breast tissue from patients operated for breast cancer.
Bmi-1 mRNA level is consistently increased and Mel-18 mRNA level is consistently decreased in adjacent normal breast tissue of cancer patients as compared to normal breast tissue in women having had reduction mammoplasties. Bmi-1/Mel-18 ratio can be potentially used as a tool for stratifying women at risk of developing malignancy.
多梳组（PcG）蛋白是参与维持细胞身份的表观遗传沉默子，其失调可导致癌症。已经研究了 Mel-18 和 Bmi-1 在肿瘤组织中的表达，但尚未在相邻的非癌性乳腺上皮中研究。我们的研究比较了癌症患者正常乳腺上皮中这两种基因的表达，并将其与相应肿瘤以及健康女性乳腺上皮中的表达水平相关联。
共研究了 79 个肿瘤，其中 71 个是乳腺癌恶性肿瘤，6 个是纤维腺瘤，2 个是 DCIS，并与 11 名健康女性的缩乳标本进行了比较。此外，23 个恶性肿瘤有可用的无癌旁组织。组织样本储存在 RNAlater 中，RNA 被分离以创建表达微阵列谱。然后，使用微阵列（Agilent 44 K）和定量 RT-PCR（TaqMan）更仔细地研究了这两个基因的 mRNA 转录水平，然后使用免疫组织化学研究了蛋白质表达水平。
与非癌症患者的正常乳腺组织相比，乳腺癌患者的相邻正常乳腺组织中 Bmi-1 mRNA 显著上调。相反，与来自乳房成形术的乳腺组织相比，来自接受乳腺癌手术的患者的正常乳腺中的 Mel-18 mRNA 转录水平较低。当评估这两个基因的蛋白质表达时，我们观察到两组组织样本中的大多数上皮细胞均为 Bmi-1 阳性，尽管与乳房成形术组织样本相比，癌症患者的正常组织中的表达强度更强。与来自接受乳腺癌手术的患者的正常乳腺组织相比，来自乳房成形术的组织样本中 Mel-18 的蛋白表达显示出相反的强度增加。
与接受缩乳术的女性的正常乳腺组织相比，癌症患者的相邻正常乳腺组织中的 Bmi-1 mRNA 水平持续升高，而 Mel-18 mRNA 水平持续降低。Bmi-1/Mel-18 比值可作为分层发生恶性肿瘤风险妇女的潜在工具。
