Skp2 mRNA在乳腺癌组织中的表达及其与ER和c-erbB-2的关系

目的探讨组织中S期激酶相关蛋白2(S-phase kinase-associated protein2,Skp2)mRNA的表达及其与雌激素受体(estrogen receptor,ER)和c-erbB-2的关系。方法采用逆转录聚合酶链反应法检测41例乳腺癌患者瘤体及癌旁正常组织中Skp2mRNA的表达情况,同时采用免疫组织化学SP法检测瘤体石蜡切片中ER和c-erbB-2的表达情况。结果瘤体组织中Skp2mRNA的表达水平明显高于癌旁正常组织(P<0.01),同时与ER表达以及临床分期、病理学分级、淋巴结转移等临床病理因素有关(P<0.05),与c-erbB-2表达、远端转移和局部复发无关(P>0.05)。结论Skp2mRNA异常表达与乳腺肿瘤发生发展有关。     

子宫内膜异位症患者异位及在位内膜的L-plastin与雌激素受体的表达及相关性研究

目的:探讨子宫内膜异位症(内异症)患者L-plastin与雌激素受体的表达及二者的相关性在内异症发生、发展中的意义。方法:采用RT-PCR方法及免疫组化S-P法检测L-plastin及雌激素受体在内异症患者的在位和异位内膜及正常子宫内膜中的表达,并对二者表达的相关性进行分析。结果:L-plastin在内异症患者在位及异位内膜中的表达水平均高于正常子宫内膜(P<0.05),且其在异位内膜中的表达水平高于在位内膜(P<0.05);雌激素受体在内异症患者在位及异位子宫内膜中的表达强于正常子宫内膜(P<0.05),且其在在位内膜中的表达强于异位内膜(P<0.05)。结论:L-plastin和雌激素受体在子宫内膜异位症患者在位及异位内膜中均表达增高,且呈正相关。L-plastin可能通过与ER结合在子宫内膜异位症发生、发展中发挥作用。L-plastin可能是与雌激素代谢相关的子宫内膜异位症特异性靶基因。     

Therapeutic advances in BIG3‐PHB2 inhibition targeting the crosstalk between estrogen and growth factors in breast cancer

Our previous studies demonstrated that specific inhibition of the BIG3‐PHB2 complex, which is a critical modulator in estrogen (E2) signaling, using ERAP, a dominant negative peptide inhibitor, leads to suppression of E2‐dependent estrogen receptor (ER) alpha activation through the reactivation of the tumor suppressive activity of PHB2. Here, we report that ERAP has significant suppressive effects against synergistic activation caused by the crosstalk between E2 and growth factors associated with intrinsic or acquired resistance to anti‐estrogen tamoxifen in breast cancer cells. Intrinsic PHB2 released from BIG3 by ERAP effectively disrupted each interaction of membrane‐associated ERα and insulin‐like growth factor 1 receptor beta (IGF‐1Rβ), EGFR, PI3K or human epidermal growth factor 2 (HER2) in the presence of E2 and the growth factors IGF or EGF, followed by inhibited the activation of IGF‐1Rβ, EGFR or HER2, and reduced Akt, MAPK and ERα phosphorylation levels, resulting in significant suppression of proliferation of ERα‐positive breast cancer cells in vitro and in vivo. More importantly, combined treatment with ERAP and tamoxifen led to a synergistic suppression of signaling that was activated by crosstalk between E2 and growth factors or HER2 amplification. Taken together, our findings suggest that the specific inhibition of BIG3‐PHB2 is a novel potential therapeutic approach for the treatment of tamoxifen‐resistant breast cancers activated by the crosstalk between E2 and growth factor signaling, especially in premenopausal women.     

Acsl4在浸润性乳腺癌组织中的表达及其临床意义

目的:探讨Acsl4在浸润性乳腺癌组织中的表达及其临床意义。方法:采用免疫组织化学法检测108例浸润性乳腺癌组织中Acsl4的表达。结果:108例浸润性乳腺癌组织中,33例(30.6%)阳性表达,75例(69.4%)阴性表达。组织学G3级的乳腺癌组织中Acsl4阳性率为42.3%(22/52),高于G1+G2级的阳性率(19.6%,11/56),差异具有统计学意义(P<0.05)。ER阳性组织的Acsl4的阳性率15.8%(6/38),低于ER阴性的病例(38.6%,27/70),差异具有统计学意义(P<0.05)。Acsl4的表达与患者年龄、肿瘤大小、淋巴结是否转移、HER2、PR、p53、Ki67的表达情况无统计学意义的相关性(P均>0.05)。结论:Acsl4在浸润性乳腺癌组织中存在异常表达,其阳性表达与乳腺癌患者组织学分级较高及ER阴性表达密切相关。