Bièche Ivan, Lerebours Florence, Tozlu Sengül, Espie Marc, Marty Michel, Lidereau Rosette
Laboratoire d'Oncogénétique - INSERM E0017, Centre René Huguenin, St-Cloud, France.
Clin Cancer Res. 2004 Oct 15;10(20):6789-95. doi: 10.1158/1078-0432.CCR-04-0306.
Inflammatory breast cancer (IBC) is a rare but particularly aggressive form of primary breast cancer. The molecular mechanisms responsible for IBC are largely unknown.
To obtain further insight into the molecular pathogenesis of IBC, we used real-time quantitative reverse transcription (RT)-PCR to quantify the mRNA expression of 538 selected genes in IBC relative to non-IBC.
Twenty-seven (5.0%) of the 538 genes were significantly up-regulated in IBC compared with non-IBC. None were down-regulated. The 27 up-regulated genes mainly encoded transcription factors (JUN, EGR1, JUNB, FOS, FOSB, MYCN, and SNAIL1), growth factors (VEGF, DTR/HB-EGF, IGFBP7, IL6, ANGPT2, EREG, CCL3/MIP1A, and CCL5/RANTES) and growth factor receptors (TBXA2R, TNFRSF10A/TRAILR1, and ROBO2). We also identified a gene expression profile, based on MYCN, EREG, and SHH, which discriminated subgroups of IBC patients with good, intermediate, and poor outcome.
Our study has identified a limited number of signaling pathways that require inappropriate activation for IBC development. Some of the up-regulated genes identified here could offer useful diagnostic or prognostic markers and could form the basis of novel therapeutic strategies.
炎性乳腺癌（IBC）是一种罕见但侵袭性特别强的原发性乳腺癌。IBC的分子机制在很大程度上尚不清楚。
为了进一步深入了解IBC的分子发病机制，我们使用实时定量逆转录（RT）-PCR来定量IBC中538个选定基因相对于非IBC的mRNA表达。
与非IBC相比，538个基因中有27个（5.0%）在IBC中显著上调。没有基因下调。27个上调基因主要编码转录因子（JUN、EGR1、JUNB、FOS、FOSB、MYCN和SNAIL1）、生长因子（VEGF、DTR/HB-EGF、IGFBP7、IL6、ANGPT2、EREG、CCL3/MIP1A和CCL5/RANTES）以及生长因子受体（TBXA2R、TNFRSF10A/TRAILR1和ROBO2）。我们还基于MYCN、EREG和SHH确定了一种基因表达谱，该谱可区分预后良好、中等和较差的IBC患者亚组。
我们的研究确定了有限数量的信号通路，IBC的发展需要这些通路的不适当激活。这里鉴定出的一些上调基因可能提供有用的诊断或预后标志物，并可构成新治疗策略的基础。
