Krajewski S, Thor A D, Edgerton S M, Moore D H, Krajewska M, Reed J C
The Burnham Institute, La Jolla, California 92037, USA.
Clin Cancer Res. 1997 Feb;3(2):199-208.
Bax and Bcl-2 are proteins that regulate programmed cell death and apoptosis. The expression of these proteins can be regulated, at least in part, by the tumor suppressor p53, but the effects of p53 are highly tissue specific. In an effort to better understand the relation between p53 and the in vivo control of the expression of Bax and Bcl-2 in adenocarcinomas of the breast, we evaluated by immunohistochemistry the expression of Bcl-2 and Bax in 149 invasive ductal carcinomas, 135 of which were chosen because of their p53 immunopositivity. The percentages of Bcl-2-immunopositive tumor cells were significantly lower in the p53-positive (median 20%) subsets as compared to the p53-negative (median 85%) subsets (P = 0. 004). Comparisons of the percentages of p53-immunopositive tumor cells with the percentages of Bcl-2- and Bax-positive cells (as continuous variables) revealed a significant inverse correlation between Bcl-2 and p53 (r = -0.41, P < 0.001) but not between Bax and p53. In the p53-positive subset, the percentages of Bax- and Bcl-2-immunopositive tumor cells were correlated positively (r = 0. 27, P = 0.002), suggesting that the expression of these genes may be co-regulated to some extent in these breast cancers. Higher percentages of Bcl-2-positive tumor cells were also associated with estrogen receptor positivity (P = 0.03), low histological tumor grade (P = 0.03), and low T stage (P = 0.02), whereas Bax immunostaining was associated only with c-erbB-2 immunopositivity (P = 0.02). Although the number of cases was small and treatment was non-uniform, preliminary correlations with clinical outcome data suggest that the prognostic significance of Bcl-2 may be enhanced by inclusion of Bax data in patients with p53-immunopositive adenocarcinoma of the breast, at least for patients with node-negative disease. Taken together, these data suggest that, despite the ability of p53 to bind directly to the Bax gene promoter, the regulation of Bax in human breast cancers does not necessarily correlate with p53 status, implying that regulation of this pro-apoptotic gene in these tumors is complex and probably influenced by several factors.
Bax和Bcl-2是调节程序性细胞死亡和凋亡的蛋白质。这些蛋白质的表达至少部分受肿瘤抑制因子p53的调控，但p53的作用具有高度的组织特异性。为了更好地理解p53与乳腺癌中Bax和Bcl-2表达的体内调控之间的关系，我们通过免疫组织化学评估了149例浸润性导管癌中Bcl-2和Bax的表达，其中135例因p53免疫阳性而被选取。与p53阴性亚组（中位数85%）相比，p53阳性亚组（中位数20%）中Bcl-2免疫阳性肿瘤细胞的百分比显著更低（P = 0.004）。将p53免疫阳性肿瘤细胞的百分比与Bcl-2和Bax阳性细胞的百分比（作为连续变量）进行比较，结果显示Bcl-2与p53之间存在显著的负相关（r = -0.41，P < 0.001），而Bax与p53之间无相关性。在p53阳性亚组中，Bax和Bcl-2免疫阳性肿瘤细胞的百分比呈正相关（r = 0.27，P = 0.002），这表明在这些乳腺癌中，这些基因的表达可能在一定程度上受到共同调控。较高百分比的Bcl-2阳性肿瘤细胞还与雌激素受体阳性（P = 0.03）、低组织学肿瘤分级（P = 0.03）和低T分期（P = 0.02）相关，而Bax免疫染色仅与c-erbB-2免疫阳性（P = 0.02）相关。尽管病例数量较少且治疗不统一，但与临床结局数据的初步相关性表明，在p53免疫阳性的乳腺腺癌患者中，至少对于无淋巴结转移的患者，将Bax数据纳入可能会增强Bcl-2的预后意义。综上所述，这些数据表明，尽管p53能够直接结合Bax基因启动子，但在人类乳腺癌中，Bax的调控不一定与p53状态相关，这意味着在这些肿瘤中，这种促凋亡基因的调控是复杂的，可能受多种因素影响。
