McIntosh G G, Anderson J J, Milton I, Steward M, Parr A H, Thomas M D, Henry J A, Angus B, Lennard T W, Horne C H
Department of Pathology, Royal Victoria Infirmary, University of Newcastle upon Tyne, UK.
Oncogene. 1995 Sep 7;11(5):885-91.
Cyclin D1 plays a critical role in the timing of the initiation of DNA synthesis in the normal cell cycle of mammalian cells. Deregulated expression of this protein has been seen in a variety of tumours either as a result of gene amplification or chromosomal translocation, in breast cancer and B cell malignancies respectively. In order to determine the role this putative oncoprotein plays in breast cancer, we have applied a new monoclonal antibody, recently produced in our laboratory, in an immunohistochemical study of 93 primary breast carcinomas. We show that approximately 28% of the cases displayed enhanced expression of the cyclin D1 protein. Furthermore, either cyclin D1, cyclin D3, or both, were expressed in 69% of cases, suggesting that overexpression of any one member of this family may relieve cancer cells of their mitogenic stimulatory requirement. In addition, we show that those patients whose breast cancers co-express cyclin D1 with either epidermal growth factor receptor (EGFR) or the retinoblastoma protein (pRB) have a significantly poorer prognosis in comparison to those expressing cyclin D1 alone. Our observations indicate that, in a subset of breast cancers, aberrant cyclin D1 expression is a contributory factor to tumorigenesis and in association with EGFR or pRB expression, identify those tumours which may require more aggressive therapy.
细胞周期蛋白D1在哺乳动物细胞正常细胞周期中DNA合成起始的时间调控方面发挥着关键作用。在多种肿瘤中均可见到该蛋白的表达失调，分别是由于基因扩增或染色体易位所致，在乳腺癌和B细胞恶性肿瘤中表现各异。为了确定这种假定的癌蛋白在乳腺癌中所起的作用，我们应用了一种最近在我们实验室制备的新型单克隆抗体，对93例原发性乳腺癌进行了免疫组织化学研究。我们发现，约28%的病例显示细胞周期蛋白D1蛋白表达增强。此外，69%的病例中细胞周期蛋白D1或细胞周期蛋白D3，或两者均有表达，这表明该家族中任何一个成员的过表达都可能使癌细胞不再需要有丝分裂刺激。此外，我们还发现，与仅表达细胞周期蛋白D1的患者相比，乳腺癌同时表达细胞周期蛋白D1与表皮生长因子受体（EGFR）或视网膜母细胞瘤蛋白（pRB）的患者预后明显更差。我们的观察结果表明，在一部分乳腺癌中，异常的细胞周期蛋白D1表达是肿瘤发生的一个促成因素，并且与EGFR或pRB表达相关，可识别出那些可能需要更积极治疗的肿瘤。
