Shen Dejun, Nooraie Farzad, Elshimali Yahya, Lonsberry Victor, He Jianbo, Bose Shikha, Chia David, Seligson David, Chang Helena R, Goodglick Lee
Gonda/UCLA Breast Cancer Research Laboratory, Revlon/UCLA Breast Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Hum Pathol. 2006 Dec;37(12):1583-91. doi: 10.1016/j.humpath.2006.06.001. Epub 2006 Aug 10.
Annexin A1 (ANXA1) is a calcium- and phospholipid-binding protein and a known mediator of glucocorticoid-regulated inflammatory responses. Using a combined multiple high-throughput approach, we recently identified a reduced expression of ANXA1 in human breast cancer. The finding was confirmed at the gene level by quantitative reverse transcription-polymerase chain reaction and at the protein level by immunohistochemical staining of normal, benign, and malignant breast tissues. In this study, we constructed and used a high-density human breast cancer tissue microarray to characterize the expressional pattern of ANXA1 according to histopathologies. The tissue microarray contains 1,158 informative breast tissue cores of different histologies including normal tissues, hyperplasia, in situ and invasive tumors, and lymph node metastases. Our results showed that there was a significant decrease in glandular expression of ANXA1 in ductal carcinoma in situ and invasive ductal carcinoma compared with either normal breast tissue or hyperplasia (P < .0001). Moreover, in benign breast tissue, myoepithelial cells showed strong expression of ANXA1. There was a decrease of ANXA1 expression in myoepithelial cells in ductal carcinoma in situ lesions compared with the same cell population in either normal or hyperplastic lesions. These results suggest that suppressed ANXA1 expression in breast tissue is correlated with breast cancer development and progression.
膜联蛋白A1(ANXA1)是一种钙和磷脂结合蛋白,是已知的糖皮质激素调节炎症反应的介质。我们最近采用多种高通量方法相结合,发现人类乳腺癌中ANXA1表达降低。这一发现通过定量逆转录-聚合酶链反应在基因水平得到证实,并通过对正常、良性和恶性乳腺组织进行免疫组织化学染色在蛋白水平得到证实。在本研究中,我们构建并使用了高密度人类乳腺癌组织芯片,以根据组织病理学特征描述ANXA1的表达模式。该组织芯片包含1158个不同组织学类型的信息丰富的乳腺组织芯块,包括正常组织、增生、原位癌和浸润性肿瘤以及淋巴结转移灶。我们的结果显示,与正常乳腺组织或增生组织相比,原位导管癌和浸润性导管癌中ANXA1的腺上皮表达显著降低(P <.0001)。此外,在良性乳腺组织中,肌上皮细胞显示出ANXA1的强表达。与正常或增生性病变中的相同细胞群体相比,原位导管癌病变中的肌上皮细胞中ANXA1表达降低。这些结果表明,乳腺组织中ANXA1表达受抑制与乳腺癌的发生和发展相关。