Influence of IFN-gamma and its receptors in human breast cancer.

Influence of IFN-gamma and its receptors in human breast cancer.
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IFN-GAMMA及其受体在人类乳腺癌中的影响。

DOI:
10.1186/1471-2407-7-158
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发表时间:
2007-08-14
期刊:
影响因子:
3.8
通讯作者:
Royuela M
Royuela M
中科院分区:
医学2区
文献类型:
--
作者:
García-Tuñón I;Ricote M;Ruiz A A;Fraile B;Paniagua R;Royuela M

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干扰素是一组触发多种反应的蛋白质,包括阻止病毒复制、抑制细胞生长和调节细胞分化。在不同的乳腺癌细胞系中,干扰素γ诱导生长停滞于G1期中期。目前,还没有关于人体乳房的活体研究。本研究旨在通过免疫印迹和免疫组织化学方法检测干扰素γ及其两种受体(干扰素γ-Rα和干扰素γ-Rβ)在不同类型乳腺癌(原位癌和浸润性癌)中的表达,以探讨其在不同类型乳腺癌中的作用。对纤维囊性病变、原位肿瘤和浸润性肿瘤三组乳腺组织中干扰素γ及其受体类型(干扰素γ-Rα和干扰素γ-Rβ)、细胞增殖(增殖细胞核抗原,又称增殖细胞核抗原)和细胞凋亡(TUNEL法)进行免疫组织化学和半定量研究。在3组患者中,干扰素γ和干扰素γ-Rα免疫反应出现在胞浆中,干扰素γ-Rβ也出现在细胞核中。原位癌中干扰素γ的光密度高于良性肿瘤和浸润性肿瘤。当我们观察干扰素γ-Rα时,浸润性癌的光密度低于良性肿瘤和原位肿瘤(密度较高)。对于干扰素γ-Rβ,三组样本的光密度值相似。在肿瘤标本中,增殖细胞核抗原和原位末端标记物指数明显高于良性病变。肿瘤恶性程度越高,增殖细胞核抗原指数越高。不同肿瘤类型之间的TUNEL结果无显著差异。干扰素γ有望成为乳腺癌的一种潜在的治疗手段。然而,肿瘤细胞在肿瘤早期能够逃脱这种细胞因子的控制,这可能是由于干扰素γ的表达减少,也可能是由于其受体或某些转导元件的改变。我们的结论是,表达干扰素γ和干扰素γ-Rα的阳性样本百分比的减少以及干扰素γ-Rβ的核定位,可能是一种肿瘤细胞反应,尽管可能不足以抑制失控的细胞增殖。也许,干扰素γ可能无法激活p21来阻止细胞周期,这表明可能参与了乳腺癌的发生。
Interferons are a group of proteins that trigger multiple responses including prevention of viral replication, inhibition of cell growth, and modulation of cell differentiation. In different mammary carcinoma cell lines IFNγ induces growth arrest at mid-G1. At the present there are no in vivo studies in human breast. The aim of this study was to investigate the expression patterns of IFNγ and its two receptors (IFNγ-Rα and IFNγ-Rβ) by Western blot and immunohistochemistry, in order to elucidate its role in the different types of human breast cancer (in situ and infiltrative). Immunohistochemical and semiquantitative study of IFNγ, its receptors types (IFNγ-Rα and IFNγ-Rβ), cell proliferation (proliferating cell nuclear antigen, also named PCNA), and apoptosis (TUNEL method) was carried between the three breast groups (fibrocystic lesions, in situ tumors and infiltrating tumors). In the three groups of patients, IFNγ and IFNγ-Rα immunoreactions appeared in the cytoplasm while IFNγ-Rβ also was found in the nucleus. The optical density to IFNγ was higher in in situ carcinoma than in benign and infiltrating tumors. When we observed IFNγ-Rα, the optical density was lower in infiltrating carcinoma than in benign and in situ tumors (the higher density). To IFNγ-Rβ, the optical density was similar in the three group samples. In tumor samples PCNA and TUNEL index was significantly higher; than in benign diseases. PCNA index increased with the malignance. No significant differences were found between cancer types to TUNEL. IFNγ could be a potential therapeutic tool in breast cancer. However, tumor cells are able to escape from the control of this cytokine in the early tumor stages; this is probably due to a decreased expression of IFNγ, or also to an alteration of either its receptors or some transduction elements. We conclude that the decrease in the % positive samples that expressed IFNγ and IFNγ-Rα together with the nuclear localization of IFNγ-Rβ, could be a tumoral cell response, although perhaps insufficient to inhibit the uncontrolled cell proliferation. Perhaps, IFNγ might be unable to activate p21 to stop the cell cycle, suggesting a possible participation in breast cancer development.
DOI: 10.1093/emboj/18.5.1223
发表时间: 1999-03-01
期刊: EMBO JOURNAL
影响因子: 11.4
作者:
Asada, M;Yamada, T;Mizutani, S
通讯作者: Mizutani, S
DOI: 10.1042/bj20020184
发表时间: 2002-08-01
影响因子: 4.1
作者:
Ruiz-Ruiz, C;López-Rivas, A
通讯作者: López-Rivas, A
DOI: 10.1016/1074-7613(94)90087-6
发表时间: 1994-09-01
期刊: IMMUNITY
影响因子: 32.4
作者:
DIGHE, AS;RICHARDS, E;SCHREIBER, RD
通讯作者: SCHREIBER, RD
DOI: 10.1016/s0959-8049(96)00273-0
发表时间: 1996-12-01
影响因子: 8.4
作者:
Mueller, H;Flury, N;Eppenberger, U
通讯作者: Eppenberger, U
DOI: 10.1089/107999001753289569
发表时间: 2001-11-01
影响因子: 2.3
作者:
Subramaniam, PS;Green, MM;Johnson, HM
通讯作者: Johnson, HM