Estrogen/EGF receptor interactions in breast cancer: rationale for new therapeutic combination strategies

Lichtner, Rosemarie B.

doi:10.1016/j.biopha.2003.09.006

Cited by 41 publications

(36 citation statements)

References 34 publications

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“…Arpino et al (2008) reviewed the cross-talk between oestrogen receptor (ER) and the HER tyrosine kinase receptor family, and proposed a mechanism of resistance to endocrine therapy in breast cancer. Inhibition of ER expression or oestradiol deprivation or treatment with anti-oestrogen increased EGFR expression in breast cancer cell lines, suggesting a complex control mechanism (Lichtner, 2003;Osborne et al, 2005) An oestrogen-independent growth ensues through alternative mechanisms during oestrogen deprivation or anti-oestrogen treatment. Upregulation of EGFR in response to oestrogen depletion was considered to be one of the survival mechanisms of tumour cells (Yarden et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor expression escapes androgen regulation in prostate cancer: a potential molecular switch for tumour growth

2009

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Androgen deprivation therapy reduces prostate cancer (PCa) tumour growth; however, disease relapse often ensues independently of androgen stimulation, producing androgen-refractory tumours with increased invasion, proliferation, and malignancy. Androgens downregulate epidermal growth factor receptor (EGFR) in normal prostate but not in PCa. Thus, loss of EGFR regulation and altered signalling may, in part, explain the transition of prostate tumours from androgen dependent to androgen independent. Studies in animal models, PCa cell lines, and tumour specimens suggest that androgens modulate prostate growth and function through mechanisms that involve 'cross-talk' between androgen receptor (AR) and growth factor receptor signalling pathways. The objective of this review is to discuss the paradoxical relationship between androgen regulation of EGFR in normal prostate and PCa. We reviewed the literature from mid-1980s through 2009 to assess the relationship between androgens and EGFR function in modulating the growth of normal prostate and PCa. Loss of androgen regulation of EGFR in PCa may be responsible for increased tumour growth, invasion, and metastasis, with important implications on the clinical management of PCa. We advance the hypothesis that a molecular switch, responsible for downregulating EGFR expression by androgens in the normal prostate, is either lost or modified in PCa.

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Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor expression escapes androgen regulation in prostate cancer: a potential molecular switch for tumour growth

2009

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“…Thus, our data also suggest the novel hypothesis that effects of PRL (and possibly other ERK-activating cytokines) on breast cancer cells could in part be related to modulation of EGF signaling by alteration of EGFR trafficking. As both PRL and EGF are potentially manipulatable targets in breast cancer (Nicholson et al, 2001;Chen et al, 2002;Clevenger et al, 2003;Lichtner, 2003;Harari, 2004;Laskin and Sandler, 2004;Goffin et al, 2005), this hypothesis is worthy of further testing in both cellular reconstitution systems and in vivo models.…”

Section: Discussionmentioning

confidence: 99%

Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor receptor in human T47D breast cancer cells

Huang

Jiang

et al. 2006

Oncogene

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Prolactin (PRL) is a polypeptide hormone produced by the anterior pituitary gland and other sites that acts both systemically and locally to cause lactation and other biological effects by interacting with the PRL receptor, a Janus kinase (JAK)2-coupled cytokine receptor family member, and activating downstream signal pathways. Recent evidence suggests PRL is a player in the pathogenesis and progression of breast cancer. Epidermal growth factor (EGF) also has effects on breast tissue, working through its receptors, epidermal growth factor receptor (EGFR) and ErbB-2 (c-neu, HER2), both intrinsic tyrosine kinase growth factor receptors. EGFR promotes pubertal breast ductal morphogenesis in mice, and both EGFR and ErbB-2 are relevant in pathogenesis and behavior of breast and other human cancers. Previous studies showed that PRL and EGF synergize to enhance motility in the human breast cancer cell line, T47D. In this study, we explored crosstalk between the PRL and EGF signaling pathways in T47D cells, with an ultimate aim of understanding how these two important factors might work together in vivo to affect breast cancer behavior. Both PRL and EGF caused robust signaling in T47D cells; PRL acutely activated JAK2, signal transducer and activator of transcription-5 (STAT5), and extracellular signal-regulated kinase-1 and -2 (ERK1 and ERK2), whereas EGF caused EGFR activation and consequent src homology collagen (SHC) activation and ERK activation. Notably, PRL also caused phosphorylation of the EGFR and ErbB-2 at sites detected by PTP101, an antibody that recognizes threonine phosphorylation at consensus motifs for ERK-induced phosphorylation. PRL-induced PTP101-reactive phosphorylation was prevented by pretreatment with PD98059, an ERK pathway inhibitor. Furthermore, PRL synergized with EGF in activating SHC and ERK and transactivating a luciferase reporter driven by c-fos gene enhancer elements, suggesting that PRL allowed markedly enhanced EGF signaling. This was accompanied by substantial inhibition of EGF-induced EGFR downregulation when PRL and EGF cotreatment was compared to EGF treatment alone. This effect of PRL was abrogated by ERK pathway inhibitor pretreatment. Our data suggest that PRL synergistically augments EGF signaling in T47D breast cancer cells at least in part by lessening EGF-induced EGFR downregulation and that this effect requires PRL-induced ERK activity and threonine phosphorylation of EGFR.

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“…Effective treatment of estrogen receptor positive (ER 1 ) BCa with antiestrogenic drugs, such as tamoxifen, is well established, however, breast carcinomas are known to eventually become refractory to hormone therapy. 2 In this study, we focus on determining the mechanism of action of a potent chemotherapeutic agent, diosgenin, on BCa cells.…”

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confidence: 99%

Diosgenin targets Akt‐mediated prosurvival signaling in human breast cancer cells

Srinivasan

Koduru

Kumar

et al. 2009

Intl Journal of Cancer

127

105

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In recent years, Akt signaling has gained recognition for its functional role in more aggressive, therapy‐resistant malignancies. As it is frequently constitutively active in cancer cells, several drugs are being investigated for their ability to inhibit Akt signaling. The purpose of this study is to determine effect of diosgenin (fenugreek), a dietary compound on Akt signaling and its downstream targets on estrogen receptor positive (ER+) and estrogen receptor negative (ER−) breast cancer (BCa) cells. Diosgenin inhibits pAkt expression and Akt kinase activity without affecting PI3 kinase levels, resulting in the inhibition of its downstream targets, NF‐κB, Bcl‐2, survivin and XIAP. The Raf/MEK/ERK pathway, another functional downstream target of Akt, was inhibited by diosgenin in ER+ but not in ER− BCa cells. Additionally, we found that diosgenin caused G1 cell cycle arrest by downregulating cyclin D1, cdk‐2 and cdk‐4 expression in both ER+ and ER− BCa cells resulting in the inhibition of cell proliferation and induction of apoptosis. Interestingly, no significant toxicity was seen in the normal breast epithelial cells (MCF‐10A) following treatment with diosgenin. Additionally, in vivo tumor studies indicate diosgenin significantly inhibits tumor growth in both MCF‐7 and MDA‐231 xenografts in nude mice. Thus, these results suggest that diosgenin might prove to be a potential chemotherapeutic agent for the treatment of BCa. © 2009 UICC

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Estrogen/EGF receptor interactions in breast cancer: rationale for new therapeutic combination strategies

Cited by 41 publications

References 34 publications

Epidermal growth factor receptor expression escapes androgen regulation in prostate cancer: a potential molecular switch for tumour growth

Epidermal growth factor receptor expression escapes androgen regulation in prostate cancer: a potential molecular switch for tumour growth

Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor receptor in human T47D breast cancer cells

Diosgenin targets Akt‐mediated prosurvival signaling in human breast cancer cells

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