Salo A, Servomaa K, Kiuru A, Pulkkinen J, Grénman R, Pekkola-Heino K, Rytömaa T
Finnish Centre for Radiation and Nuclear Safety, Helsinki, Finland.
Acta Otolaryngol Suppl. 1997;529:233-6.
The bcl-2 oncogene was originally found in the translocation in a pre-B cell acute lymphocytic leukemia cell line. Since then a high expression of Bcl-2 has been found in many types of cancer. The bcl-2 gene encodes an intracellular membrane-associated protein. Overexpression of bcl-2 inhibits apoptosis induced by many drugs and radiation. In this study the bcl-2 gene status of 9 human head and neck squamous cell carcinoma cell lines was studied. Mutations of the bcl-2 gene were studied at mRNA and DNA levels. The presence and abundance of the Bcl-2 protein in cells were also investigated. In earlier studies the p53 tumour suppressor gene was screened for point mutations, and the radiosensitivity of these cell lines was measured. We were able to amplify bcl-2 cDNA from 5 of the 9 cell lines, which shows that bcl-2 was expressed in these cells. No point mutations were found in the bcl-2 gene in any of these cell lines. Loss of heterozygosity was observed in 2 cell lines at the bcl-2 locus, and these cell lines had no detectable levels of bcl-2 mRNA or Bcl-2 protein. The Bcl-2 protein was abundant in the cell lines with the wild-type p53 gene, and these cell lines were radioresistant. The Bcl-2 protein was also found in many other cell lines in mitotic cells. It seems that cells expressing bcl-2 are radioresistant, and even functional p53 cannot induce apoptosis in these cells.
bcl-2癌基因最初是在一种前B细胞急性淋巴细胞白血病细胞系的易位中发现的。从那时起，在许多类型的癌症中都发现了Bcl-2的高表达。bcl-2基因编码一种细胞内膜相关蛋白。bcl-2的过表达抑制了许多药物和辐射诱导的细胞凋亡。在本研究中，对9个人类头颈部鳞状细胞癌细胞系的bcl-2基因状态进行了研究。在mRNA和DNA水平上研究了bcl-2基因的突变。还研究了细胞中Bcl-2蛋白的存在和丰度。在早期研究中，筛选了p53肿瘤抑制基因的点突变，并测量了这些细胞系的放射敏感性。我们能够从9个细胞系中的5个扩增出bcl-2 cDNA，这表明bcl-2在这些细胞中表达。在任何这些细胞系的bcl-2基因中均未发现点突变。在2个细胞系的bcl-2基因座处观察到杂合性缺失，并且这些细胞系没有可检测到的bcl-2 mRNA或Bcl-2蛋白水平。Bcl-2蛋白在具有野生型p53基因的细胞系中丰富，并且这些细胞系具有放射抗性。在有丝分裂细胞中的许多其他细胞系中也发现了Bcl-2蛋白。似乎表达bcl-2的细胞具有放射抗性, 并且即使功能性p53也不能在这些细胞中诱导细胞凋亡。
