Bcl-2 phosphorylation has pathological significance in human breast cancer
Bcl-2 phosphorylation has pathological significance in human breast cancer
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DOI：
10.1159/000096022
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发表时间：
2006-01-01
期刊：
影响因子：
5
通讯作者：
Konishi, Noboru
中科院分区：
文献类型：
--
作者：
Matsuyoshi, Syuichi;Shimada, Keiji;Konishi, Noboru
众所周知，抗凋亡分子Bcl-2在乳腺癌的化疗耐药中起着重要作用。我们之前已经证明，通过c-jun nh2末端激酶（JNK）激活Fasassociated death domain containing protein （FADD）在194丝氨酸的磷酸化，通过加速G2/M的细胞周期阻滞，使乳腺癌细胞对化疗敏感，并且JNK/FADD下游的Bcl-2磷酸化在紫杉醇抑制细胞生长中起重要作用。本研究采用免疫组织化学方法，分析了磷酸化Bcl-2 （P-Bcl-2）与雌激素、孕激素、c-erbB-2受体、p53表达和磷酸化FADD/JNK （P-FADD/JNK）之间的紧密病理关联。P-Bcl-2的表达与淋巴浸润、淋巴结转移显著相关，但与组织学分化、肿瘤分级、血管和脂肪浸润无关。P-Bcl-2的阳性与P-FADD/JNK的阳性也显著相关。因此，PBcl-2以及P-FADD/JNK参数可能是人类乳腺癌中独立于激素受体状态的癌症进展的有用标记物。版权所有(c) 2006 S. Karger AG，巴塞尔。
The anti-apoptotic molecule, Bcl-2, is well known to play an important role in the chemoresistance of breast cancer. We have previously demonstrated that phosphorylation of Fasassociated death domain-containing protein (FADD) at 194 serine through c-jun NH2-terminal kinase (JNK) activation sensitizes breast cancer cells to chemotherapy through accelerating cell cycle arrest at G2/M, and that Bcl-2 phosphorylation downstream of JNK/FADD plays an important role in cell growth suppression by paclitaxel. In this study, the clink copathological association of phosphorylated Bcl-2 (P-Bcl-2) with estrogen, progesterone, c-erbB-2 receptors, p53 expressions and phosphorylated FADD/JNK (P-FADD/JNK) was analyzed immunohistochemically using 107 human breast cancer specimens. Expression of P-Bcl-2 was found to significantly correlate with lymphatic invasion, lymph node metastasis, but not histological differentiation, tumor grade or vascular and fatty invasion. The positivity of P-Bcl-2 was also significantly correlated to that of P-FADD/JNK. Thus, PBcl-2 as well as the P-FADD/JNK parameter might be useful markers for cancer progression, independent of the hormone receptor status, in human breast cancers. Copyright (c) 2006 S. Karger AG, Basel.