Stable transfection of an estrogen receptor beta cDNA isoform into MDA-MB-231 breast cancer cells

Tonetti, Debra A.; Rubenstein, Robyn; Deleon, M.; Zhao, Huifang; Pappas, Sam G.; Bentrem, David J.; Chen, Bin; Constantinou, Andreas I.; Jordan, V. Craig

doi:10.1016/j.jsbmb.2003.07.003

Cited by 51 publications

(53 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, these two important angiogenic factors may not play a role in ERb-transfected cells which have more lung metastasis. Tonetti et al (2003) findings as ours and they reported that with Erb protein expression increasing the cell proliferation rate accelerated (Tonetti et al, 2003 However, all of these studies showed that the effects of ERb on tumor cells were all estradiol-independent, which suggested that there exist some new pathways to activate ERb.…”

Section: Discussionmentioning

confidence: 61%

ERβ exerts multiple stimulative effects on human breast carcinoma cells

Hou

Yuan

et al. 2004

Oncogene

View full text Add to dashboard Cite

Recent studies of ERs in breast cancer have demonstrated the existence of ERb in addition to ERa. Some clinical data indicated that ERb had prognostic value for patient's survival, which suggested that ERb plays a key role in breast cancer development and metastasis. To test this hypothesis, we generated an ERb high-expression cell line by reintroduced human ERb cDNA into MDA-MB-435 cells. We demonstrated that ERb exerted multiple tumor-stimulative effects on human breast carcinoma cells both in vivo and in vitro. In in vitro studies, ERb was able to increase the proliferation and invasion of MDA-MB-435 cells significantly, while these effects were totally estradiol independent. Also, this stimulation was characterized by downregulation of p21 and upregulation of MMP-9, as well as transcriptional factor Est-1. In in vivo studies, we also demonstrated that ERb-transfected MDA-MB-435 cells grew much faster and had more pulmonary metastasis than mock or wild-type cells in nude mice. In ERb-transfected MDA-MB-435 xenografts, ERb caused significant reduction in p21 protein levels. Similar effects of ERb on MMP-9 and Ets-1 expression noted in vitro studies were also observed in the in vivo studies. These in vitro and in vivo studies indicated that ERb exerted multiple stimulative effects on breast cancer development and metastasis.

show abstract

Section: Discussionmentioning

confidence: 61%

ERβ exerts multiple stimulative effects on human breast carcinoma cells

Hou

Yuan

et al. 2004

Oncogene

View full text Add to dashboard Cite

show abstract

“…Most cell line models in which ERb1 has been stably expressed either inducibly or constitutively show that overexpression of ERb1 inhibits proliferation irrespective of whether it is coexpressed with ERa (Paruthiyil et al, 2004;Strom et al, 2004;Murphy et al, 2005) or not (Lazennec et al, 2001;Cheng et al, 2004). However, two studies using cell line models have been published in which stable constitutive overexpression of ERb1 resulted in increased proliferation (Tonetti et al, 2003;Hou et al, 2004) although in the former publication the short form of ERb1 (truncated by 45 amino acids from the N-terminus) was used. Both breast cancer cell lines used (MDA-MB-231 and MDA-MB-435) are typically ERa negative and therefore can be considered to represent the ERb alone expressing breast tumours cohort in vivo.…”

Section: Discussionmentioning

confidence: 99%

Expression of oestrogen receptor-β in oestrogen receptor-α negative human breast tumours

et al. 2006

View full text Add to dashboard Cite

To analyse the phenotype of breast tumours that express oestrogen receptor-b (ERb) alone tissue microarrays were used to investigate if ERb isoforms are associated with specific prognostic markers and gene expression phenotypes in ERa-negative tumours. ERa-negative tumours were positive for ERb1 in 58% of cases (n ¼ 122/210), total ERb in 60% (n ¼ 115/192) and ERb2/cx in 57% of cases (n ¼ 114/199). Oestrogen receptor-b1 and total ERb were significantly correlated with Ki67 (r ¼ 0.28, Po0.0001, n ¼ 209; r ¼ 0.29, Po0.0001, n ¼ 191) and with CK5/6, a marker of the basal phenotype (r ¼ 0.20, P ¼ 0.0106, n ¼ 170; r ¼ 0.18, P ¼ 0.0223, n ¼ 158). ERb2/cx was strongly associated with p-c-Jun and NF-kBp65 (r ¼ 0.53, Po0.0001, n ¼ 93; r ¼ 0.35, Po0.0001, n ¼ 176). This study shows that a range of ERb isoform expression occurs in ERa-negative breast tumours. While expression of ERb1, total and ERb2/cx are correlated, individual forms show associations with certain phenotypes that suggest different roles in subsets of ERanegative cancers. Based on our in vivo observations, ERb may have the potential to become a therapeutic target in the specific subcohort of ERa-negative breast cancers.

show abstract

“…ER 1 over-expression alone in the absence of ER -negative MDAMB231 human breast cancer cells has resulted in variable results with both growth inhibition (Lazennec et al 2001) and growth stimulation being reported (Tonetti et al 2003). However, when over-expression of ER 1 in an ER -positive background has been achieved, more consistent results have been obtained, and in particular over-expressed ER 1 results in growth inhibition (Paruthiyil et al 2004, Strom et al 2004.…”

Section: Over-expression Of Er-1 In Mcf7 Cells · L C Murphy and Othermentioning

confidence: 99%

Inducible upregulation of oestrogen receptor-β1 affects oestrogen and tamoxifen responsiveness in MCF7 human breast cancer cells

Murphy

Peng²,

Lewis³

et al. 2005

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

To investigate the effect of altered oestrogen receptor (ER) and ER expression on oestrogen and anti-oestrogen action in breast cancer, we have stably expressed an inducible ER 1 in MCF7 breast cancer cells. Stably expressing clones were isolated and over-expression of ER 1 correlated with increased levels of specific radiolabelled oestradiol (E2) binding. Increased ER 1 did not affect endogenous levels of ER but increased progesterone receptor (PR) levels. Over-expression of ER 1 reduced growth responses to E2 in contrast to little if any effect of over-expression of ER . In oestrogen-replete conditions, over-expression of ER 1 but not ER reduced proliferation. Over-expression of ER 1 did not result in anti-oestrogen resistance but was associated with increased sensitivity to 4-hydroxytamoxifen. Our results suggested that over-expression of ER 1 in the presence of an endogenously expressed ER was associated with tamoxifen sensitivity but may negatively modulate ER -mediated growth. However, not all ER activities were inhibited since endogenous PR expression was increased by both ER and ER 1 over-expression. These data paralleled those seen in some in vivo studies showing a relationship between PR and ER expression as well as ER expression and tamoxifen sensitivity of ER-positive breast cancer patients. These models are relevant and will be useful for dissecting the role of ER 1 expression in ER-positive breast cancer.

show abstract

Stable transfection of an estrogen receptor beta cDNA isoform into MDA-MB-231 breast cancer cells

Cited by 51 publications

References 44 publications

ERβ exerts multiple stimulative effects on human breast carcinoma cells

ERβ exerts multiple stimulative effects on human breast carcinoma cells

Expression of oestrogen receptor-β in oestrogen receptor-α negative human breast tumours

Inducible upregulation of oestrogen receptor-β1 affects oestrogen and tamoxifen responsiveness in MCF7 human breast cancer cells

Contact Info

Product

Resources

About