Epidermal growth factor receptor and c-erbB-2 expression in normal breast tissue during the menstrual cycle

Gompel, Anne; Martin, Anne Marie; Simon, Petra; Schöevaërt, Damien; Plu‐Bureau, Geneviève; Hugol, D.; Audouin, J; Leygue, Etienne; Truc, J B; Poitout, P

doi:10.1007/bf01806677

Cited by 39 publications

(24 citation statements)

References 27 publications

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“…Progesterone and Type I Growth Factor Receptors-All four type I receptor tyrosine kinase family members are expressed in normal and malignant breast epithelial cells (17), and are under steroid hormone regulation (45,46). Here, we show that the levels of at least three family members (EGFR, c-ErbB2, and c-ErbB3) are up-regulated by progesterone (Fig.…”

Section: Fig 4 Progesterone Enhances Mapk Activation By Egfmentioning

confidence: 55%

Convergence of Progesterone and Epidermal Growth Factor Signaling in Breast Cancer

Lange

Richer

Shen

et al. 1998

Journal of Biological Chemistry

180

118

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During late stages of breast cancer progression, tumors frequently acquire steroid hormone resistance with concurrent amplification of growth factor receptors; this alteration predicts a poor prognosis. We show here that following treatment with the progestin, R5020, breast cancer cells undergo a "biochemical shift" in the regulation of epidermal growth factor (EGF)-stimulated signaling pathways: R5020 potentiates the effects of EGF by up-regulating EGFR, c-ErbB2 and c-ErbB3 receptors, and by enhancing EGF-stimulated tyrosine phosphorylation of signaling molecules known to associate with activated type I receptors. Independently of EGF, R5020 increases Stat5 protein levels, association of Stat5 with phosphotyrosine-containing proteins, and tyrosine phosphorylation of JAK2 and Shc. Furthermore, progestins "prime" breast cancer cells for growth signals by potentiating EGF-stimulated p42/p44 mitogenactivated protein kinase (MAPK), p38 MAP kinase, and JNK activities. Although the levels of cyclin D1, cyclin E, and p21 WAF1 , are up-regulated by R5020 alone, they are synergistically up-regulated by EGF in the presence of R5020. Up-regulation of cell cycle proteins by EGF is blocked by inhibition of p42/p44 MAPK only in the presence of R5020, supporting a shift in the regulation of these cell cycle mediators from MAPK-independent to MAPK-dependent pathways. In summary, progesterone selectively increases the sensitivity of key kinase cascades to growth factors, thereby priming cells for stimulation by latent growth signals. These data support a model in which breast cancer cell growth switches from steroid hormone to growth factor dependence.Estradiol and progesterone are involved in breast cancer development, but at the time of diagnosis only one-third of tumors are steroid hormone-dependent. As they progress, these tumors often acquire steroid hormone resistance, yet retain nuclear steroid receptors. Indeed, nuclear receptor loss or mutation accounts for only 10 -20% of steroid hormone-resistant tumors (1). Thus, it has been postulated that in the majority of resistant tumors, control over growth is assumed by locally acting autocrine or paracrine peptide growth factors. As a result, invasive cancers with the worst prognosis are those that are growth factor receptor positive and steroid hormone resistant (2). Growth factors regulate cell growth by activating intracellular signal transduction pathways after binding to high affinity tyrosine kinase receptors on the cell surface. Steroid hormone receptors are ligand-activated nuclear transcription factors. Herein, we sought to understand how these two separate pathways converge to regulate breast cancer cell growth.The mechanisms by which growth factors stimulate cell proliferation are complex. Growth factors induce receptor dimerization and activation of intrinsic tyrosine kinase activity. Autophosphorylation of tyrosine residues located in the cytoplasmic domain of the receptors stimulates binding of specific regulatory proteins via their SH2 1 and SH3 domains, which ...

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Section: Fig 4 Progesterone Enhances Mapk Activation By Egfmentioning

confidence: 55%

Convergence of Progesterone and Epidermal Growth Factor Signaling in Breast Cancer

Lange

Richer

Shen

et al. 1998

Journal of Biological Chemistry

180

118

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“…(Reproduced with permission from Gandhi et al 2000. ) Role of growth factor receptors in ER-negative ductal carcinoma in situ ER-negative DCIS has been shown to express type 1 tyrosine kinase growth factor receptors, such as EGFR and c-erbB-2 (Hanna et al 1990, Pavelic et al 1992, Bobrow & Millis 1995, Gompel et al 1996, Robertson et al 1996. Both EGFR and c-erbB-2 have an extracellular receptor binding domain and a cytoplasmic tyrosine kinase domain.…”

Section: Relevance Of Anti-oestrogen Therapy Findings To the Clinicalmentioning

confidence: 99%

“…EGFR is a 170 kDa transmembrane glycoprotein expressed on many epithelial cells (Gompel et al 1996). It is activated by at least six ligands, including epidermal growth factor (EGF), transforming growth factor (TGF)-α and heparin-binding EGF.…”

Section: Relevance Of Anti-oestrogen Therapy Findings To the Clinicalmentioning

confidence: 99%

“…Therefore, evidence is accumulating that the EGFR is the main receptor pathway associated with epithelial proliferation in the human breast (Gompel et al 1996). c-erbB-2 is a 185 kDa transmembrane tyrosine kinase with considerable homology to EGFR, and for which a ligand has not yet been identified.…”

Section: Wwwendocrinologyorgmentioning

confidence: 99%

“…Moreover, frequent co-expression of transcripts for both c-erbB-2 and c-erbB-3 has recently been found in a series of primary breast tumours (Siegel et al 1999). Therefore, metastasis may result from c-erbB-2/c-erbB-3 heterodimers, although the low expression of c-erbB-2 in normal breast suggests that DCIS development involves EGFR rather than c-erbB-2 (Gompel et al 1996).…”

Section: Wwwendocrinologyorgmentioning

confidence: 99%

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Studies of epidermal growth factor receptor inhibition in breast cancer.

Bundred¹,

Chan²,

Anderson³

2001

Endocrine-Related Cancer

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Until recently, there has been little knowledge on the growth control of oestrogen receptor (ER)-negative ductal carcinoma in situ (DCIS) and invasive breast cancer. The recent development of DCIS models, such as transgenic mice, cell-line xenograft models and, importantly, in vivo human DCIS xenograft models has facilitated the investigation and understanding of the control of growth of early pre-invasive breast lesions.Recent studies have shown that ER-negative DCIS, unlike ER-positive DCIS, is hormone independent and does not respond to anti-oestrogen treatment. Moreover, DCIS of the comedo type utilises type I tyrosine kinase growth factors, such as epidermal growth factor receptor (EGFR) and c-erbB-2, in receptor signalling for growth. New data underscore the importance of EGFR as the major modulating growth factor receptor in the control of proliferation in the breast.Pre-clinical studies performed on human DCIS xenografts in nude mice suggest a potential role for EGFR tyrosine kinase inhibitors (EGFR-TKIs). More specifically, ZD1839, a novel orally active and selective EGFR-TKI, has been shown to produce a response in DCIS through a decrease in epithelial proliferation. These findings have enhanced our knowledge of signal transduction pathways in cancer and indicate that tyrosine kinase blockade of EGFR has potential for the treatment and chemoprevention of DCIS.It is hoped that further advances in this area and evaluation of EGFR-TKIs in Phase II/III clinical trials will allow their therapeutic potential as anticancer agents to be appreciated.

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Expression of c-erbB receptors, heregulin and oestrogen receptor in human breast cell lines

et al. 2000

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Epidermal growth factor receptor and c-erbB-2 expression in normal breast tissue during the menstrual cycle

Cited by 39 publications

References 27 publications

Convergence of Progesterone and Epidermal Growth Factor Signaling in Breast Cancer

Convergence of Progesterone and Epidermal Growth Factor Signaling in Breast Cancer

Studies of epidermal growth factor receptor inhibition in breast cancer.

Expression of c-erbB receptors, heregulin and oestrogen receptor in human breast cell lines

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