van Slooten H J, van de Vijver M J, van de Velde C J, van Dierendonck J H
Department of Surgery, Leiden University Medical Centre, The Netherlands.
Br J Cancer. 1998 Mar;77(5):789-96. doi: 10.1038/bjc.1998.128.
Bcl-2 has been demonstrated to inhibit apoptosis in breast cancer cells in vitro, and the ratio between Bcl-2 and its proapoptotic homologue Bax seems to be an important determinant of cellular sensitivity to induction of apoptosis. However, little information is available on the relationship between Bcl-2 and the rate of apoptotic and necrotic cell death in breast tumours. From a series of 441 premenopausal, lymphnode-negative breast cancer patients, a subset of 49 tumours was selected in which immunostaining for the 26-kDa isoform of Bcl-2 was either absent (n = 23) or very high (n = 26). High expression of Bcl-2 was found to be strongly associated with low rates of apoptotic (P < 0.001) and necrotic cell death (P < 0.001). The mean value of the apoptotic index was 2.69%+/-1.40% in Bcl-2-negative tumours and 0.68%+/-1.00% in Bcl-2-positive tumours. Expression of the proapoptotic protein Bax correlated neither with Bcl-2 nor with the frequency of apoptotic cells. Immunostaining for the antiapoptotic Bcl-2 homologue BcI-X(L) correlated with Bcl-2 expression (P < 0.001) but not with apoptosis. High proliferation rate and high tumour grade (Bloom-Richardson) were strongly associated with absence of Bcl-2 expression (P< 0.001). p53 accumulation was associated with absence of Bcl-2 expression and increased apoptotic activity. Loss of Bcl-2 expression was strongly correlated with increased apoptotic and necrotic cell death, high proliferation rate and high tumour grade, supporting a model in which Bcl-2 not only mediates cell death, but also cell division in breast cancer tissue, and in which regulation of cell division and cell death are tightly linked.
Bcl-2已被证明在体外可抑制乳腺癌细胞的凋亡，Bcl-2与其促凋亡同源物Bax之间的比例似乎是细胞对凋亡诱导敏感性的重要决定因素。然而，关于Bcl-2与乳腺肿瘤中凋亡和坏死性细胞死亡速率之间的关系，目前所知甚少。在441例绝经前、淋巴结阴性的乳腺癌患者中，选取了49个肿瘤的子集，其中26-kDa Bcl-2亚型的免疫染色要么缺失（n = 23），要么非常高（n = 26）。发现Bcl-2的高表达与低凋亡率（P < 0.001）和坏死性细胞死亡率（P < 0.001）密切相关。Bcl-2阴性肿瘤的凋亡指数平均值为2.69%±1.40%，Bcl-2阳性肿瘤为0.68%±1.00%。促凋亡蛋白Bax的表达与Bcl-2以及凋亡细胞的频率均无相关性。抗凋亡Bcl-2同源物BcI-X(L)的免疫染色与Bcl-2表达相关（P < 0.001），但与凋亡无关。高增殖率和高肿瘤分级（Bloom-Richardson）与Bcl-2表达缺失密切相关（P < 0.001）。p53积聚与Bcl-2表达缺失及凋亡活性增加相关。Bcl-2表达缺失与凋亡和坏死性细胞死亡增加、高增殖率和高肿瘤分级密切相关，支持了一种模型，即Bcl-2不仅介导乳腺癌组织中的细胞死亡，还介导细胞分裂，且细胞分裂和细胞死亡的调节紧密相连。
