Rosenberg C L, Motokura T, Kronenberg H M, Arnold A
Endocrine Unit, Massachusetts General Hospital, Boston 02114.
Oncogene. 1993 Feb;8(2):519-21.
PRAD1 (cyclin D1) is a recently identified member of the family of cyclin genes, believed to play roles in regulating transitions through the cell cycle. The PRAD1 gene, located at 11q13, has been implicated in the pathogenesis of a variety of tumors, including parathyroid adenomas, t(11;14) bearing B-lymphoid tumors (particularly centrocytic lymphomas) where it is highly likely to be the BCL1 oncogene, and possibly in breast carcinomas and squamous cell cancers of the head and neck as well. PRAD1's tumorigenic influence appears to be effected through overexpression of its normal-sized transcript, but it has not been established whether the transcript's coding sequence is normal or contains oncogenic mutations. We have sequenced the coding region of the overexpressed PRAD1 transcript from two primary tumors with clonal PRAD1 region rearrangements: a benign parathyroid adenoma and a malignant centrocytic lymphoma. Each sequence is identical to the normal PRAD1 cDNA sequence, and presumably encodes normal PRAD1 protein. Thus, PRAD1 likely functions as a direct-acting oncogene whose rearrangement in tumors leads to overexpression or deregulated expression of its normal protein product.
PRAD1（细胞周期蛋白D1）是细胞周期蛋白基因家族中最近发现的成员，被认为在调节细胞周期转换中发挥作用。PRAD1基因位于11q13，与多种肿瘤的发病机制有关，包括甲状旁腺腺瘤、携带t(11;14)的B淋巴细胞肿瘤（特别是中心细胞淋巴瘤），在这些肿瘤中它很可能是BCL1癌基因，也可能与乳腺癌以及头颈部鳞状细胞癌有关。PRAD1的致瘤影响似乎是通过其正常大小转录本的过表达实现的，但尚未确定该转录本的编码序列是正常的还是包含致癌突变。我们对来自两个具有克隆性PRAD1区域重排的原发性肿瘤（一个良性甲状旁腺腺瘤和一个恶性中心细胞淋巴瘤）中过表达的PRAD1转录本的编码区进行了测序。每个序列都与正常的PRAD1 cDNA序列相同，推测编码正常的PRAD1蛋白。因此，PRAD1可能作为一种直接作用的癌基因，其在肿瘤中的重排导致其正常蛋白产物的过表达或表达失调。
