Regulation of Fas ligand expression in breast cancer cells by estrogen: functional differences between estradiol and tamoxifen

Mor, Gil; Kohen, Förtüne; García-Velasco, Juan A.; Nilsen, Jon; Brown, Wendi; Song, J. J.; Naftolin, Frederick

doi:10.1016/s0960-0760(00)00081-9

Cited by 75 publications

(55 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly to the present study, the authors showed that stimulated tumour cells induced apoptosis of isolated T lymphocytes more effectively than their unstimulated controls (Meng et al, 2004). Additional factors, which regulate FasL in tumour cells, include oestrogen and the anti-oestrogen factor tamoxifen tested on human breast cancer cells (Mor et al, 2000), and the bacterial polysaccharide exotoxin CM101 tested on murine melanoma cells (Yakes et al, 2000). The results of the present study suggest that tumour-produced CRH might be an autocrine -paracrine factor, which together with others, modulates the expression of FasL in ovarian cancer.…”

Section: Discussionsupporting

confidence: 74%

Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation

et al. 2007

View full text Add to dashboard Cite

Although corticotropin-releasing hormone (CRH) and Fas ligand (FasL) have been documented in ovarian carcinoma, a clear association with tumour progression and immuno-escape has not been established. FasL plays an important role in promoting tumour cells' ability to counterattack immune cells. Here, we examined immunohistochemically the expression of CRH, CRHR1, CRHR2 and FasL in 47 human ovarian cancer cases. The ovarian cancer cell lines OvCa3 and A2780 were further used to test the hypothesis that CRH might contribute to the immune privilege of ovarian tumours, by modulating FasL expression on the cancer cells. We found that CRH, CRHR1, CRHR2 and FasL were expressed in 68.1, 70.2, 63.8 and 63.8% of the cases respectively. Positivity for CRH or FasL expression was associated with higher tumour stage. Finally, CRH increased the expression of FasL in OvCa3 and A2780 cells through CRHR1 thereby potentiated their ability to induce apoptosis of activated peripheral blood lymphocytes. Corticotropinreleasing hormone produced by human ovarian cancer might favour survival and progression of the tumour by promoting its immune privilege. These findings support the hypothesis that CRHR1 antagonists could potentially be used against ovarian cancer.

show abstract

Section: Discussionsupporting

confidence: 74%

Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation

et al. 2007

View full text Add to dashboard Cite

show abstract

“…46 Estrogen may increase the mitotic activity of the cells and the number of DNA replication errors. 36,47,48 Mor et al 49 showed that FASL in breast tissue was functionally active and that FASL expression was regulated by estrogen, possibly as a result of a putative estrogen receptor response element in the FASL promoter region. Estrogen has also been shown to trigger T-cell apoptosis by upregulating FAS and FASL in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

The FAS ligand promoter polymorphism, rs763110 (−844C>T), contributes to cancer susceptibility: evidence from 19 case–control studies

et al. 2009

View full text Add to dashboard Cite

The potentially functional polymorphism, rs763110 (À844C4T), in the promoter region of the FAS ligand (FASL) gene, has been implicated in cancer risk, but individually published studies show inconclusive results. To derive a more precise estimation of the association between the FASL rs763110 and risk of cancer, we performed a meta-analysis of 19 published studies that included 11 105 cancer cases and 11 372 controls. We used odds ratios (ORs) and 95% confidence intervals (CIs) to assess the strength of the associations. Overall, the rs763110 CT and TT variant genotypes were associated with a significantly reduced cancer risk of all cancer types in different genetic models (homozygote comparison: OR ¼ 0.80, 95% CI: 0.68-0.95, P heterogeneity ¼ 0.001; heterozygote comparison: OR ¼ 0.82, 95% CI: 0.72 -0.95, P heterogeneity o0.001; dominant model comparison: OR ¼ 0.82, 95% CI: 0.71 -0.94, P heterogeneity o0.001; and recessive model comparison: OR ¼ 0.88, 95% CI: 0.81 -0.96, P heterogeneity ¼ 0.074). In the stratified analyses, the risk remained for studies of the smoking-related cancers and Asian populations, or population-based studies in all the genetic models. Although some modest bias could not be eliminated, this meta-analysis suggests that the FASL rs763110 T allele has a possible protective effect on cancer risk.

show abstract

“…Recently, it was shown that estrogen regulates FasL expression in breast and ovarian cancer cells, suggesting that a possible estrogenic effect on monocyte survival may also be mediated through the regulation of FasL expression (32,52). However, this effect could be indirect through the expression of cytokines or growth factors.…”

Section: Discussionmentioning

confidence: 99%

“…Details of the characterization for the RT-PCR have been described previously (31,32). Briefly, reverse transcription was performed using the RT-PCR kit from Amersham Pharmacia Biotech (Piscataway, NJ) according to the manufacturer's directions.…”

Section: Rt-pcrmentioning

confidence: 99%

Interaction of the Estrogen Receptors with the Fas Ligand Promoter in Human Monocytes

Mor

Sapi

Abrahams

et al. 2003

The Journal of Immunology

Self Cite

165

View full text Add to dashboard Cite

The predominance of autoimmune diseases among women suggests that estrogen may modulate immune function. Monocytes and macrophages are important in initiating, maintaining, and resolving inflammatory responses through cell-signaling molecules, which control immune cell survival. One important mechanism of cell survival is mediated by the Fas/Fas ligand (FasL) system. In this study, the link between estrogen, monocytes/macrophages, and the Fas/FasL system was investigated. Estrogen treatment increased FasL expression in monocytes through the binding of the estrogen receptors (ER) to the estrogen recognizing elements and AP-1 motifs present at the FasL promoter. Furthermore, estrogen induced apoptosis in monocytes expressing ERβ, but not in monocyte-differentiated macrophages expressing ERα. The expression of either ERα or ERβ and their response to estrogen in monocytes was found to be dependent on the their stage of cell differentiation. Previously, we have shown that estrogen replacement therapy in postmenopausal women decreased the number of circulating monocytes. In this study, we have characterized the molecular mechanism by which estrogen regulates monocytes homeostasis. These findings indicate that estrogen may regulate immune cell survival through the Fas/FasL system. There is biological relevance to these findings in view of studies showing that accumulation of activated monocytes is involved in the pathogenesis of conditions such as vasculititis, arteriosclerosis, and rheumatoid arthritis.

show abstract

Regulation of Fas ligand expression in breast cancer cells by estrogen: functional differences between estradiol and tamoxifen

Cited by 75 publications

References 46 publications

Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation

Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation

The FAS ligand promoter polymorphism, rs763110 (−844C>T), contributes to cancer susceptibility: evidence from 19 case–control studies

Interaction of the Estrogen Receptors with the Fas Ligand Promoter in Human Monocytes

Contact Info

Product

Resources

About