bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group study.

Elledge, Richard M.; Green, S.; Howes, L. G.; Clark, Gary M.; Berardo, Melora D.; Allred, D. Craig; Pugh, Reginald P.; Ciocca, Daniel R.; Ravdin, Peter M.; Rivkin, Saul E.; Martino, S; Osborne, C. Kent

doi:10.1200/jco.1997.15.5.1916

Cited by 184 publications

(161 citation statements)

References 20 publications

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…Downregulation of BCL-2 is involved in antiestrogeninduced apoptosis and depletion of BCL-2 expression enhances sensitivity of breast cancer cells to tamoxifen (Diel et al, 1999;Zhang et al, 1999;Kim et al, 2005). BCL-2 is positively associated with ERa expression (Elledge et al, 1997) whereas decreased BCL-2 expression has been observed after induction of ERb expression in T47D mammary carcinoma cells (Williams et al, 2008), concordant with our observation that ERb is decreased and BCL-2 expression is increased by forced expression of ARTN.…”

Section: Discussionsupporting

confidence: 88%

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

et al. 2010

View full text Add to dashboard Cite

We have previously identified an oncogenic role of artemin (ARTN), a member of glial cell derived neurotrophic factor family of ligands, in mammary carcinoma. We herein report that ARTN is an estrogen-inducible gene. Metaanalysis of gene expression data sets showed that ARTN expression is positively correlated to estrogen receptor (ER) status in human mammary carcinoma. Furthermore, in patients with ER-positive mammary carcinoma treated with tamoxifen, high ARTN expression is significantly correlated with decreased survival. Forced expression of ARTN in ER-positive human mammary carcinoma cells increased ER transcriptional activity, promoted estrogenindependent growth and produced resistance to tamoxifen and fulvestrant in vitro and to tamoxifen in xenograft models. ARTN-stimulated resistance to tamoxifen and fulvestrant is mediated by increased BCL-2 expression. Conversely, depletion of endogenous ARTN by smallinterfering RNA or functional antagonism of ARTN by antibody enhanced the efficacy of antiestrogens. Tamoxifen decreased ARTN expression in tamoxifen-sensitive mammary carcinoma cells whereas ARTN expression was increased in tamoxifen-resistant cells and not affected by tamoxifen treatment. Antibody inhibition of ARTN in tamoxifen-resistant cells improved tamoxifen sensitivity. Functional antagonism of ARTN therefore warrants consideration as an adjuvant therapy to enhance antiestrogen efficacy in ER-positive mammary carcinoma.

show abstract

Section: Discussionsupporting

confidence: 88%

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Our present results also suggested that HER2/neu level and hormonal receptor expression was inversely correlated. This finding is supported by the Southwest Oncology Group Study and Konecney Report (Elledge et al, 1998;Ferrero-Pous et al, 2000;Konecny et al, 2003). While previous studies have reported HER2/ neu to be a poor prognostic factor (Slamon et al, 1989;Quenel et al, 1995), neither CAV1, CAV2, nor HER2/neu appeared to be a predictor of disease outcome in our study.…”

Section: Discussionsupporting

confidence: 86%

Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer

et al. 2004

View full text Add to dashboard Cite

Caveolin-1 and -2 (CAV1, CAV2) are closely linked genes localised to the fragile region of 7q31 (FRA7G), and loss of heterozygosity involving this region has been reported in breast cancer. Several studies have suggested that CAV1 is a negative regulator of HER2/ neu signal transduction in vitro. However, the clinical significance of CAV1 in breast cancer has not yet been clarified. We examined quantitatively the mRNA levels of CAV1, CAV2 and HER2/neu in 162 cases of breast cancer using real-time PCR. Caveolin-1 and -2 protein expression was also examined by Western blotting and immunohistochemistry. We then evaluated for correlations between CAV1, CAV2 and HER2/neu gene expression and clinicopathologic factors in the 162 breast cancer cases. Results showed higher HER2/neu mRMA levels and lower CAV1 and CAV2 mRMA levels in breast cancer tissues than in corresponding normal tissues (Po0.001). Caveolin-1 and -2 protein expression levels were also suppressed in cancer tissues compared to normal tissues by Western blotting. Immunohistochemistry revealed that CAV1 and CAV2 proteins were abundantly expressed in mammary gland myoepithelial cells, but only weakly in ductalepithelial cells. Reduced CAV1 mRNA level was significantly associated with increasing tumour size (P ¼ 0.041), and negative oestrogen receptor status (P ¼ 0.021). There was also a significant association between low CAV2 mRNA level and negative progesterone receptor status (P ¼ 0.013), and between high HER2/neu mRNA level and negative hormonal receptor status (ER, P ¼ 0.029, PgR, P ¼ 0.019). While there was no relationship between HER2/neu and CAV1 mRNA levels, a significant association between CAV1 and CAV2 mRNA levels was observed (Po0.001). Our results indicated that CAV1 suppression correlated closely with that of CAV2 in breast cancer, that CAV1 level was inversely correlated with tumour size, and that CAV1 and CAV2 levels were correlated with hormonal receptor status. Therefore, CAV1 and CAV2 play an important role in tumour progression in breast cancer patients.

show abstract

“…Furthermore, they all lack PR expression (Lykkesfeldt et al, 1994(Lykkesfeldt et al, , 1995. Several clinical studies have shown that the Bcl-2 expression in breast tumours is strongly correlated to both ERα and PR expression, and Bcl-2 expression is an indicator of a favourable outcome following endocrine treatment (Gee et al, 1994;Lipponen et al, 1995;Silvestrini et al, 1996;Elledge et al, 1997;Keen et al, 1997;Kobayashi et al, 1997;Olopade et al, 1997;Holmqvist et al, 1999). The decreased Bcl-2 expression associated with decreased ERα expression, and lack of response to antioestrogens observed in the resistant cell lines is in concert with the above-mentioned clinical studies.…”

Section: Discussionmentioning

confidence: 99%

Anti-oestrogen resistant human breast cancer cell lines are more sensitive towards treatment with the vitamin D analogue EB1089 than parent MCF-7 cells

2001

View full text Add to dashboard Cite

Summary Most breast cancer patients treated with anti-oestrogens will eventually develop resistance towards treatment. Therefore it is important to find new therapeutic agents effective for treatment of patients relapsing on anti-oestrogen. The vitamin D analogue EB1089 (Seocalcitol TM ) is a promising new agent for treatment of breast cancer patients with advanced disease, and in this study we show that two different anti-oestrogen-resistant human breast cancer cell lines are more sensitive towards treatment with EB1089, than the parent MCF-7 cell line. The two resistant cell lines both express a lower content of the anti-apoptotic protein Bcl-2, and we suggest that this may explain the higher sensitivity towards EB1089. The importance of Bcl-2 for response to EB1089 is supported by our observation that oestradiol abrogates the effect of EB1089 in cell lines which increase Bcl-2 in response to oestradiol treatment. Overall these results indicate that treatment with Seocalcitol TM may prove effective when patients become refractory to anti-oestrogen therapy, and that Bcl-2 may be used as a predictive marker.

show abstract

bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group study.

Cited by 184 publications

References 20 publications

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer

Anti-oestrogen resistant human breast cancer cell lines are more sensitive towards treatment with the vitamin D analogue EB1089 than parent MCF-7 cells

Contact Info

Product

Resources

About