Stålberg Peter, Granberg Dan, Carling Tobias, Wilander Erik, Eriksson Barbro, Gobl Anders, Akerström Goran, Rastad Jonas, Modlin Irvin M, Oberg Kjell, Skogseid Britt
Department of Surgical Sciences, University Hospital, S-751 85 Uppsala, Sweden.
Anticancer Res. 2003 May-Jun;23(3B):2227-32.
Phospholipase C beta 3 (PLCB3) plays an important role in the signal transduction of the seven transmembrane receptors. The gene is located in the vicinity of the Multiple Endocrine Neoplasia type 1 (MEN1) gene on chromosome 11q13. Transfection of PLCB3 to neuroendocrine cell lines lacking expression suppresses the neoplastic phenotype and affects the gene expression of S100A3 and human mismatch repair protein, suggesting a role for PLCB3 in neuroendocrine tumorigenesis.
We used RNA-RNA in situ hybridisation for PLCB3 on a total of 82 samples including 34 from MEN1 patients.
We show that the PLCB3 transcript is missing in 8 out of 14 MEN1-associated neoplasias as well as in 4 out of 10 bronchial carcinoids, 2 out of 10 exocrine pancreatic cancers and one sporadic adrenocortical carcinoma.
Low or lack of PLCB3 expression in a subset of endocrine tumours, together with earlier published in vitro data on suppressor characteristics upon transfection, indicate that PLCB3 could be involved in the tumorigenesis in a subset of endocrine tumours.
磷脂酶Cβ3(PLCB3)在七跨膜受体的信号转导中起重要作用。该基因位于11号染色体q13上的多发性内分泌肿瘤1型(MEN1)基因附近。将PLCB3转染到缺乏表达的神经内分泌细胞系中可抑制肿瘤表型,并影响S100A3和人类错配修复蛋白的基因表达,提示PLCB3在神经内分泌肿瘤发生中起作用。
我们对总共82个样本进行了PLCB3的RNA-RNA原位杂交,其中包括34个来自MEN1患者的样本。
我们发现,在14个与MEN1相关的肿瘤中有8个、10个支气管类癌中有4个、10个外分泌性胰腺癌中有2个以及1个散发性肾上腺皮质癌中,PLCB3转录本缺失。
一部分内分泌肿瘤中PLCB3表达低或缺乏,以及早期发表的关于转染后抑制特性的体外数据表明,PLCB3可能参与一部分内分泌肿瘤的肿瘤发生。