Méndez O, Máñas S, Fabra A, Escobedo A, Moreno A, Sierra A
Centro de Oncologia Molecular, Institut de Recerca Oncològica, Hospital Duran i Reynals, Ciutat Sanitaria i Universitaria de Bellvitge (CSUB), Barcelona, Spain.
Breast Cancer Res Treat. 2001 Jan;65(2):171-7. doi: 10.1023/a:1006490622103.
Metastatic progression in ductal breast carcinomas are related to apoptosis in primary tumors. Frameshift mutations in a single-repeat sequence within the coding region (G)8 of the pro-apoptotic Bax gene have been related to microsatellite instability (MSI) and progression of some carcinomas and lymphomas. The aim of this study was to explore whether the extended lifespan of breast cancer cells can also be triggered by Bax mutation in ductal-breast carcinomas, and whether breast cancer cell MSI is related to the loss of apoptosis. For this purpose we studied frameshift mutations of a microsatellite (G)8 in the third exon of the Bax gene in a series of 105 ductal breast carcinomas, at T1 and T2-3 stages, 45 of which had lymph node metastasis. We analyzed MSI in five sequences of DNA isolated from normal and tumor tissue samples taken from 86 patients, and we explored the relationship between MSI and tumor apoptosis status. Bax mutation was not present in ductal breast carcinomas. MSI (two or more markers altered) was detected in 11.6% of tumors. Loss of apoptosis occurred in 80% (8/10) tumors with MSI, versus 17.8% of tumors without MSI (chi2 test, p = 0.0004), independently of Bax protein expression. We conclude that frameshift mutations of a microsatellite (G)8 of the Bax gene are not critical for the loss of apoptosis in breast cancer, and that loss of apoptosis may be a consequence of overexpression of anti-apoptotic protein Bcl-2 or Bcl-xL. Moreover, MSI in breast carcinomas might be the cause of loss of an apoptotic pathway that is not induced by frameshift mutations of a microsatellite (G)8 of the Bax gene.
乳腺导管癌的转移进展与原发肿瘤中的细胞凋亡有关。促凋亡基因Bax编码区(G)8单重复序列中的移码突变与一些癌和淋巴瘤的微卫星不稳定性(MSI)及进展相关。本研究的目的是探讨Bax突变是否也能引发乳腺导管癌细胞寿命延长，以及乳腺癌细胞MSI是否与细胞凋亡缺失有关。为此，我们研究了105例处于T1和T2 - 3期的乳腺导管癌中Bax基因第三外显子微卫星(G)8的移码突变，其中45例有淋巴结转移。我们分析了从86例患者的正常和肿瘤组织样本中分离的五个DNA序列中的MSI，并探讨了MSI与肿瘤细胞凋亡状态之间的关系。乳腺导管癌中未发现Bax突变。11.6%的肿瘤检测到MSI(两个或更多标记改变)。MSI的肿瘤中有80%(8/10)发生细胞凋亡缺失，而无MSI的肿瘤中这一比例为17.8%(卡方检验，p = 0.0004)，与Bax蛋白表达无关。我们得出结论，Bax基因微卫星(G)8的移码突变对乳腺癌细胞凋亡缺失并不关键，细胞凋亡缺失可能是抗凋亡蛋白Bcl - 2或Bcl - xL过表达的结果。此外，乳腺癌中的MSI可能是一种凋亡途径缺失的原因，而这种缺失并非由Bax基因微卫星(G)8的移码突变所诱导。
