Advanced concepts in estrogen receptor biology and breast cancer endocrine resistance: implicated role of growth factor signaling and estrogen receptor coregulators

2005 ◽  
Vol 56 (S1) ◽  
pp. 10-20 ◽  
Author(s):  
Rachel Schiff ◽  
Suleiman A. Massarweh ◽  
Jiang Shou ◽  
Lavina Bharwani ◽  
Grazia Arpino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Growth Factor ◽  
Endocrine Resistance ◽  
Growth Factor Signaling ◽  
Receptor Biology

Resistance to endocrine therapy in breast cancer: exploiting estrogen receptor/growth factor signaling crosstalk

2006 ◽  
Vol 13 (Supplement_1) ◽  
pp. S15-S24 ◽  
Author(s):  
Suleiman Massarweh ◽  
Rachel Schiff
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Growth Factor ◽  
Endocrine Therapy ◽  
Acquired Resistance ◽  
Growth Factor Signaling ◽  
Breast Cancer Patients ◽  
Signaling Crosstalk ◽  
Receptor Modulator ◽  
Signal Transduction Inhibitors

Targeting the estrogen receptor (ER) is the oldest form of molecular targeted therapy, and the widespread use of the selective estrogen receptor modulator tamoxifen in breast cancer is responsible for major improvements in cure rates, quality of life, and disease prevention in the last 25 years. Newer forms of endocrine therapy now available for the management of endocrine responsive breast cancer include a new generation of aromatase inhibitors, which lower the estrogen ligand for ER, and pure ER antagonists which destroy the receptor. Despite these recent clinical advances, intrinsic and acquired resistance to these endocrine therapies is still a common feature that limits the success of this therapeutic strategy. Recent research into the molecular biology of ER signaling has revealed a remarkably complex interactive signaling with other growth factor signaling pathways in breast cancer cells, potentially explaining some of the reasons behind endocrine therapy action as well as resistance. This view of a more complex ER signaling system has uncovered new molecular targets which, if present in a cancer cell, might be additionally targeted using various signal transduction inhibitors to overcome or prevent resistance to endocrine therapy. In addition, the dynamic inverse relationship between the expression of ER and growth factor receptors brings more excitement to the potential of restoring ER expression in apparently ER-negative cells by inhibition of growth factor signaling. Ongoing clinical trials of endocrine therapy combined with growth factor pathway inhibitors or their downstream signaling elements promise to further improve the present care for breast cancer patients.

scholarly journals Growth factor-driven mechanisms associated with resistance to estrogen deprivation in breast cancer: new opportunities for therapy

2004 ◽  
Vol 11 (4) ◽  
pp. 623-641 ◽  
Author(s):  
R I Nicholson ◽  
C Staka ◽  
F Boyns ◽  
I R Hutcheson ◽  
J M W Gee
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Breast Cancer Cells ◽  
Endocrine Resistance ◽  
Signaling Networks ◽  
Growth Factor Signaling ◽  
Independent Manner ◽  
Estrogen Withdrawal ◽  
Current Article ◽  
The Many

There is an increasing body of evidence demonstrating that elevated growth signaling in breast cancer cells can promote forms of endocrine resistance in either an estrogen receptor-dependent or -independent manner. The current article reviews what is known about such growth factor signaling networks and resistance to estrogen withdrawal and considers the many novel therapeutic opportunities that stem from this knowledge.

scholarly journals The Role of Transforming Growth Factor-β in the Regulation of Estrogen Receptor Expression in the MCF-7 Breast Cancer Cell Line1

Endocrinology ◽  
1997 ◽  
Vol 138 (4) ◽  
pp. 1498-1505 ◽  
Author(s):  
Adriana Stoica ◽  
Miguel Saceda ◽  
Amina Fakhro ◽  
Harrison B. Solomon ◽  
Bradley D. Fenster ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Growth Factor ◽  
Breast Cancer Cell ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Receptor Expression ◽  
Estrogen Receptor Expression ◽  
Mcf 7

scholarly journals Roles for miRNAs in endocrine resistance in breast cancer

2015 ◽  
Vol 22 (5) ◽  
pp. R279-R300 ◽  
Author(s):  
Penn Muluhngwi ◽  
Carolyn M Klinge
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Aromatase Inhibitors ◽  
Estrogen Receptor Alpha ◽  
Acquired Resistance ◽  
Endocrine Resistance ◽  
Breast Cancer Patients ◽  
Initial Tumor ◽  
Bona Fide

Therapies targeting estrogen receptor alpha (ERα), including selective ER modulators such as tamoxifen, selective ER downregulators such as fulvestrant (ICI 182 780), and aromatase inhibitors such as letrozole, are successfully used in treating breast cancer patients whose initial tumor expresses ERα. Unfortunately, the effectiveness of endocrine therapies is limited by acquired resistance. The role of microRNAs (miRNAs) in the progression of endocrine-resistant breast cancer is of keen interest in developing biomarkers and therapies to counter metastatic disease. This review focuses on miRNAs implicated as disruptors of antiestrogen therapies, theirbona fidegene targets and associated pathways promoting endocrine resistance.

scholarly journals Role of estrogen receptor (ER) α in insulin-like growth factor (IGF)-I-induced responses in MCF-7 breast cancer cells

2005 ◽  
Vol 35 (3) ◽  
pp. 433-447 ◽  
Author(s):  
S Zhang ◽  
X Li ◽  
R Burghardt ◽  
R Smith ◽  
S H Safe
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Growth Factor ◽  
Breast Cancer Cells ◽  
S Phase ◽  
Induced Responses ◽  
Igf I ◽  
Phase Progression ◽  
Mcf 7

Insulin-like growth factor-I (IGF-I) is a mitogenic polypeptide that induces proliferation of MCF-7 breast cancer cells, and cotreatment with the phosphoinositide 3-kinase (PI3-K) inhibitor LY294002 and the antiestrogen ICI 182780 inhibits IGF-I-induced growth. The role of estrogen receptor α (ERα) in mediating responses induced by IGF-I was investigated in cells transfected with small inhibitory RNA for ERα (iERα). The results showed that IGF-I-dependent phosphorylation of Akt and mitogen-activated protein kinase, induction of G1–S-phase progression and enhanced expression of cyclin D1 and cyclin E were dependent on ERα. Moreover, these same IGF-I-induced responses were also inhibited by the antiestrogen ICI 182780 and this was in contrast to a previous report suggesting that ICI 182780 did not affect IGF-I-dependent activation of PI3-K or induction of cyclin D1 expression. ICI 182780 exhibits antimitogenic activity and iERα inhibits G1–S-phase progression and proliferation of MCF-7 cells treated with IGF-I, suggesting that the effects of the antiestrogen are primarily related to downregulation of ERα.

Role of receptor complexes in the extranuclear actions of estrogen receptor α in breast cancer

2006 ◽  
Vol 13 (Supplement_1) ◽  
pp. S3-S13 ◽  
Author(s):  
Robert X-D Song ◽  
Ping Fan ◽  
Wei Yue ◽  
Yucai Chen ◽  
Richard J Santen
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Plasma Membrane ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Adaptor Proteins ◽  
Estrogen Receptor Α ◽  
Mitogen Activated Protein Kinase ◽  
Receptor Complexes

Our recent studies have examined the role of various receptor complexes in the mediation of rapid, extranuclear effects of estradiol. This review describes 17β-estradiol (E2)-initiated extranuclear signaling pathways, which involve the insulin-like growth factor 1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) and result in the activation of several kinase cascades. The biologic results of these effects are the enhancement of cell proliferation and diminution of programmed cell death (apoptosis). Until recently, most studies assigned priority to the nuclear transcriptional actions of estrogen receptor α (ERα). Present investigative emphasis focuses on the additional importance of ERα residing in or near the plasma membrane. A small fraction of ERα is associated with the cell membrane and mediates the rapid effects of E2. Unlike classical growth factor receptors, such as IGF-1R and EGFR, ERα has no transmembrane and kinase domains and is known to initiate E2 rapid signals by forming protein/protein complexes with many signaling molecules. Our recent studies demonstrate that the IGF-1R is involved in tethering ERα to the plasma membrane, in activating the EGFR, and in the initiation of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling. The formation of a multi-protein complex containing these receptors as well as adaptor proteins is a critical step in this process. A full understanding of the mechanisms underlying these relationships with the ultimate aim of abrogating specific steps, should lead to more targeted strategies for treatment of hormone-dependent breast cancer.

Sign in / Sign up

Export Citation Format

Share Document