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Suppressor of cytokine signalling gene expression is elevated in breast carcinoma.

Raccurt M, Tam SP, Lau P, Mertani HC, Lambert A, Garcia-Caballero T, Li H, Brown RJ, McGuckin MA, Morel G, Waters MJ - Br. J. Cancer (2003)

Bottom Line: Recently, inducible feedback suppressors of cytokine signalling (SOCS/JAB/SSI) have been identified, which decrease cell sensitivity to cytokines.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.

View Article: PubMed Central - PubMed

Affiliation: CNRS UMR 5123, Bât. Raphael Dubois, Université Claude Bernard-Lyon 1, 43 Blvd 11 Novembre 1918, F69622 Villeurbanne cedex, France.

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.

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Lack of effect of serum on expression of CIS protein in breast cancer lines. Cells were exposed to 10% serum or serum starved for 12 h before harvesting for immunoblot analyses as for Figure 6.
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fig7: Lack of effect of serum on expression of CIS protein in breast cancer lines. Cells were exposed to 10% serum or serum starved for 12 h before harvesting for immunoblot analyses as for Figure 6.

Mentions: In order to determine if expression of the CIS protein was dependent on serum factors, including prolactin and GH, the breast cancer lines were deprived of serum for 12 h before harvesting for immunoblot analysis. As can be seen in Figure 7Figure 7


Suppressor of cytokine signalling gene expression is elevated in breast carcinoma.

Raccurt M, Tam SP, Lau P, Mertani HC, Lambert A, Garcia-Caballero T, Li H, Brown RJ, McGuckin MA, Morel G, Waters MJ - Br. J. Cancer (2003)

Lack of effect of serum on expression of CIS protein in breast cancer lines. Cells were exposed to 10% serum or serum starved for 12 h before harvesting for immunoblot analyses as for Figure 6.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2394374&req=5

fig7: Lack of effect of serum on expression of CIS protein in breast cancer lines. Cells were exposed to 10% serum or serum starved for 12 h before harvesting for immunoblot analyses as for Figure 6.
Mentions: In order to determine if expression of the CIS protein was dependent on serum factors, including prolactin and GH, the breast cancer lines were deprived of serum for 12 h before harvesting for immunoblot analysis. As can be seen in Figure 7Figure 7

Bottom Line: Recently, inducible feedback suppressors of cytokine signalling (SOCS/JAB/SSI) have been identified, which decrease cell sensitivity to cytokines.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.

View Article: PubMed Central - PubMed

Affiliation: CNRS UMR 5123, Bât. Raphael Dubois, Université Claude Bernard-Lyon 1, 43 Blvd 11 Novembre 1918, F69622 Villeurbanne cedex, France.

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.

Show MeSH
Related in: MedlinePlus