title: Suppressor of cytokine signalling gene expression is elevated in breast carcinoma.
abstract: Cytokines are important for breast cell function, both as trophic hormones and as mediators of host defense mechanisms against breast cancer. Recently, inducible feedback suppressors of cytokine signalling (SOCS/JAB/SSI) have been identified, which decrease cell sensitivity to cytokines. We examined the expression of SOCS genes in 17 breast carcinomas and 10 breast cancer lines, in comparison with normal tissue and breast lines. We report elevated expression of SOCS-1-3 and CIS immunoreactive proteins within in situ ductal carcinomas and infiltrating ductal carcinomas relative to normal breast tissue. Significantly increased expression of SOCS-1-3 and CIS transcripts was also shown by quantitative in situ hybridisation within both tumour tissue and reactive stroma. CIS transcript expression was elevated in all 10 cancer lines, but not in control lines. However, there was no consistent elevation of other SOCS transcripts. CIS protein was shown by immunoblot to be present in all cancer lines at increased levels, mainly as the 47 kDa ubiquitinylated form. A potential proliferative role for CIS overexpression is supported by reports that CIS activates ERK kinases, and by strong induction in transient reporter assays with an ERK-responsive promoter. The in vivo elevation of SOCS gene expression may be part of the host/tumour response or a response to autocrine/paracrine GH and prolactin. However, increased CIS expression in breast cancer lines appears to be a specific lesion, and could simultaneously shut down STAT 5 signalling by trophic hormones, confer resistance to host cytokines and increase proliferation through ERK kinases.
authors.affiliation: CNRS UMR 5123, Bât. Raphael Dubois, Université Claude Bernard-Lyon 1, 43 Blvd 11 Novembre 1918, F69622 Villeurbanne cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Raccurt
authors.forename: S P
authors.initials: SP
authors.lastname: Tam
authors.forename: P
authors.initials: P
authors.lastname: Lau
authors.forename: H C
authors.initials: HC
authors.lastname: Mertani
authors.forename: A
authors.initials: A
authors.lastname: Lambert
authors.forename: T
authors.initials: T
authors.lastname: Garcia-Caballero
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: R J
authors.initials: RJ
authors.lastname: Brown
authors.forename: M A
authors.initials: MA
authors.lastname: McGuckin
authors.forename: G
authors.initials: G
authors.lastname: Morel
authors.forename: M J
authors.initials: MJ
authors.lastname: Waters
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019382:Human Growth Hormone / Q000494:pharmacology; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D011388:Prolactin / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000494:pharmacology; D012097:Repressor Proteins; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D018909:src Homology Domains
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D019382:Human Growth Hormone; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011388:Prolactin; D011506:Proteins; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C108944:SOCS1 protein, human; C106643:SOCS2 protein, human; C106644:SOCS3 protein, human