Fra-1在乳腺肿瘤细胞质和细胞核同时定位相关性的研究

Association between the Simultaneous Nuclear and Cytoplasmic Localization of Fra-1 and Breast Malignancy

目的:侵袭转移是恶性肿瘤最重要也是最本质的生物学特征,是许多恶性肿瘤患者治疗失败和死亡的主要原因。最近研究发现Fra-1在细胞的运动、侵袭,维持转化细胞的恶性表型方面具有重要的作用,但是有关Fra-1在乳腺组织中的表达及Fra-1在细胞中的定位研究很少,本研究探讨转录因子Fra-1在人乳腺良、恶性肿瘤组织中的表达及细胞内的定位。方法:采用免疫组织化学方法检测良、恶性乳腺肿瘤组织Fra-1表达及细胞定位;并分析恶性乳腺肿瘤组织Fra-1表达与乳腺癌预后指标ER、PR和HER-2表达的相关性。结果:61例良、恶性肿瘤组织都存在Fra-1的细胞核表达。在20例良性肿瘤组织中,17例(85.0%)Fra-1主要定位于上皮细胞核内,3例(15.0%)可见Fra-1细胞核及细胞质共表达。而37例(90.2%)恶性肿瘤组织存在Fra-1细胞核和细胞质共表达,Fra-1在恶性肿瘤细胞质中的表达明显高于良性肿瘤(P<0.001)。恶性肿瘤Fra-1细胞质表达与ER、PR和HER-2的表达无明显相关性。结论:Fra-1蛋白的表达强度与方式与乳腺癌上皮细胞的癌变有关;其在乳腺癌细胞细胞质的滞留与乳腺癌的发生发展具有一定的相关性。

Objective： To discuss the expression and location of the transcription factor Fra-1 in benign anct mangnant numn breast tissues. Methods： Fra-1 expression was investigated immunohistochemically in neoplastic breast diseases ranging from benign fi- broadenomas to very aggressive undifferentiated carcinomas. The correlation between Fra-I expression and other indicators of breast carcinoma prognosis （ ER, PR, and ErbB2 receptors ） were analyzed. Results： The nuclei of all neoplastic breast tissue cells, both in benign and malignant breast tissues, were immunoreactive to anti-Fra-1 antibodies. In 85% of the benign tumors （ 17/20 ）, the immunoreactivity of the anti-Fra- 1 antibodies was exclusively restricted to the nuclei. In three cases （ 3/20, 15% ）, focal unequivocal cytoplasmic staining was also observed. Strong positive nuclear staining for Fra-1 was easily seen in all types of breast carcinomas. However, con- comitant nuclear-cytoplasmic immunoreactivity was observed in all types of breast carcinomas. A clear shift in Fra-1 immunoreactivity, from an exclusively nuclear to a simultaneous nuclear and cytoplasmic localization, was observed in 90.2% （ 37/41 ） of breast carcino- mas. No inverse relationship was observed between Fra-1 and the ER and PR protein levels in the malignant tumors. The relative Fra-1 expression level was not correlated with ErbB2 expression. Conclusion： The overall expression, pattern, and intensity of the Fra-1 protein were correlated with breast oncogenesis. Fra-1 overexpression, leading to persistently high cytoplasmic accumulation, may play a role in breast carcinogenesis