NF-kappa B genes have a major role in inflammatory breast cancer.
BACKGROUND
IBC (Inflammatory Breast cancer) is a rare form of breast cancer with a particular phenotype. New molecular targets are needed to improve the treatment of this rapidly fatal disease. Given the role of NF-kappaB-related genes in cell proliferation, invasiveness, angiogenesis and inflammation, we postulated that they might be deregulated in IBC.


METHODS
We measured the mRNA expression levels of 60 NF-kappaB-related genes by using real-time quantitative RT-PCR in a well-defined series of 35 IBCs, by comparison with 22 stage IIB and III non inflammatory breast cancers. Twenty-four distant metastases of breast cancer served as "poor prognosis" breast tumor controls.


RESULTS
Thirty-five (58%) of the 60 NF-kappaB-related genes were significantly upregulated in IBC compared with non IBC. The upregulated genes were NF-kappaB genes (NFKB1, RELA, IKBKG, NFKBIB, NFKB2, REL, CHUK), apoptosis genes (MCL1L, TNFAIP3/A20, GADD45B, FASLG, MCL1S, IER3L, TNFRSF10B/TRAILR2), immune response genes (CD40, CD48, TNFSF11/RANKL, TNFRSF11A/RANK, CCL2/MCP-1, CD40LG, IL15, GBP1), proliferation genes (CCND2, CCND3, CSF1R, CSF1, SOD2), tumor-promoting genes (CXCL12, SELE, TNC, VCAM1, ICAM1, PLAU/UPA) or angiogenesis genes (PTGS2/COX2, CXCL1/GRO1). Only two of these 35 genes (PTGS2/COX2 and CXCL1/GRO1)were also upregulated in breast cancer metastases. We identified a five-gene molecular signature that matched patient outcomes, consisting of IL8 and VEGF plus three NF-kappaB-unrelated genes that we had previously identified as prognostic markers in the same series of IBC.


CONCLUSIONS
The NF-kappaB pathway appears to play a major role in IBC, possibly contributing to the unusual phenotype and aggressiveness of this form of breast cancer. Some upregulated NF-kappaB-related genes might serve as novel therapeutic targets in IBC.
Lerebours
Florence
F
Centre Rene Huguenin, FNCLCC, 35 rue Dailly, 92210, St-Cloud, France. f.lerebours@stcloud-huguenin.org
Vacher
Sophie
S
Andrieu
Catherine
C
Espie
Marc
M
Marty
Michel
M
Lidereau
Rosette
R
Bieche
Ivan
I
D001706:Biopsy; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D016000:Cluster Analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000150:complications; D016328:NF-kappa B / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation
D016328:NF-kappa B; D012333:RNA, Messenger