Bargou R C, Daniel P T, Mapara M Y, Bommert K, Wagener C, Kallinich B, Royer H D, Dörken B
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
Int J Cancer. 1995 Mar 16;60(6):854-9. doi: 10.1002/ijc.2910600622.
We have studied the expression of the apoptosis-regulating genes bcl-2, bcl-x, bax and APO-1/fas (CD95) in human breast cancer. The expression pattern of these genes in human breast-cancer tissues and breast-cancer-derived cell lines was compared to that seen in normal breast epithelium and breast epithelial cell lines. No difference with regard to bcl-2 and bcl-xL expression was observed between normal breast epithelium and tumor tissue or breast cancer and non-malignant epithelial cell lines. In contrast, bax-alpha, a splice variant of bax, which promotes apoptosis, is expressed in high amounts in normal cell lines and breast tissue, whereas only weak or no expression could be detected in cancer-cell lines and malignant tissue. In contrast to malignant cell lines, which express low levels of bax-alpha, non-malignant epithelial cell lines displaying high amounts of bax-alpha were highly sensitive to induction of programmed cell death by both serum starvation and APO-1/fas (CD95) triggering. We therefore propose that dysregulation of apoptosis contributes to the pathogenesis of breast cancer, at least in part, due to an imbalance between anti-apoptosis genes (such as bcl-2/bcl-x) and apoptosis-promoting genes (bax).
我们研究了凋亡调节基因bcl-2、bcl-x、bax和APO-1/fas（CD95）在人类乳腺癌中的表达情况。将这些基因在人类乳腺癌组织和乳腺癌衍生细胞系中的表达模式，与正常乳腺上皮和乳腺上皮细胞系中的表达模式进行了比较。在正常乳腺上皮与肿瘤组织之间，以及乳腺癌与非恶性上皮细胞系之间，未观察到bcl-2和bcl-xL表达存在差异。相比之下，bax的剪接变体bax-alpha可促进细胞凋亡，在正常细胞系和乳腺组织中大量表达，而在癌细胞系和恶性组织中仅能检测到微弱表达或无表达。与表达低水平bax-alpha的恶性细胞系不同，大量表达bax-alpha的非恶性上皮细胞系对血清饥饿和APO-1/fas（CD95）触发诱导的程序性细胞死亡高度敏感。因此，我们认为凋亡失调至少部分是由于抗凋亡基因（如bcl-2/bcl-x）与促凋亡基因（bax）之间的失衡，从而导致乳腺癌的发病机制。
