Wang T C, Cardiff R D, Zukerberg L, Lees E, Arnold A, Schmidt E V
Department of Medicine, Massachusetts General Hospital, Boston 02114.
Nature. 1994 Jun 23;369(6482):669-71. doi: 10.1038/369669a0.
Physical associations between cyclins, viral oncogenes and tumour suppressor genes imply a central role for cyclins in growth control. Cyclin D1 was identified as a candidate oncogene (PRAD1) in tumour-specific DNA rearrangements and is suspected to be a contributor to several types of neoplasms including breast cancer. Cyclin D1 also rescues G1 cyclin-defective Saccharomyces cerevisiae, and is a growth-regulated gene. Despite evidence suggesting that cyclin D1 is an oncogene, its ability to transform cells directly in culture remains controversial. To evaluate its potential to deregulate growth in vivo in a physiologically relevant tissue we overexpressed cyclin D1 in mammary cells in transgenic mice. We report here that overexpression of cyclin D1 resulted in abnormal mammary cell proliferation including the development of mammary adenocarcinomas. We conclude that overexpression of cyclin D1 deregulates cell proliferation and can induce tumorigenic changes in mammary tissues, suggesting that cyclin D1 indeed plays an important oncogenic role in breast cancer.
细胞周期蛋白、病毒癌基因和肿瘤抑制基因之间的物理关联暗示了细胞周期蛋白在生长控制中起核心作用。细胞周期蛋白D1在肿瘤特异性DNA重排中被鉴定为候选癌基因（PRAD1），并且被怀疑是包括乳腺癌在内的几种肿瘤的促成因素。细胞周期蛋白D1还能拯救G1细胞周期蛋白缺陷型酿酒酵母，并且是一个生长调节基因。尽管有证据表明细胞周期蛋白D1是一种癌基因，但其在培养中直接转化细胞的能力仍存在争议。为了评估其在生理相关组织中体内失调生长的潜力，我们在转基因小鼠的乳腺细胞中过表达细胞周期蛋白D1。我们在此报告，细胞周期蛋白D1的过表达导致乳腺细胞异常增殖，包括乳腺腺癌的发生。我们得出结论，细胞周期蛋白D1的过表达会使细胞增殖失调，并可诱导乳腺组织发生致瘤性变化，这表明细胞周期蛋白D1确实在乳腺癌中发挥重要的致癌作用。
