Insulin and epidermal growth factor stimulate phosphorylation of p185HER-2 in the breast carcinoma cell line, BT474

Lin, Yuzhong J.; Li, Shiwei; Clinton, Gail M.

doi:10.1016/0303-7207(90)90004-r

Cited by 13 publications

(6 citation statements)

References 27 publications

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“…Phosphorylation of all of these growth factor signaling molecules was abolished by gefitinib. Effects of estrogen and tamoxifen on phosphorylation of downstream effectors of EGFR and HER2 similar to those in MCF-7/HER2-18 cells were observed in another cell line, BT474, which expresses ER and is naturally gene amplified for HER2 and AIB1 (19,20) (Fig. 2, B).…”

Section: Cross-talk Between Growth Factor Receptor and Er Pathwayssupporting

confidence: 53%

Mechanisms of Tamoxifen Resistance: Increased Estrogen Receptor-HER2/neu Cross-Talk in ER/HER2-Positive Breast Cancer

Shou¹,

Massarweh²,

Osborne³

et al. 2004

JNCI Journal of the National Cancer Institute

1,070

907

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Section: Cross-talk Between Growth Factor Receptor and Er Pathwayssupporting

confidence: 53%

Mechanisms of Tamoxifen Resistance: Increased Estrogen Receptor-HER2/neu Cross-Talk in ER/HER2-Positive Breast Cancer

Shou¹,

Massarweh²,

Osborne³

et al. 2004

JNCI Journal of the National Cancer Institute

1,070

907

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“…The antibody against the COOH terminus of p185HER-2 and p95HER-2 [anti-neu (C)] has been previously described (34). This antibody has been found to be much more effective in detecting p95HER-2 than most commercially available antipeptide antibodies directed against the COOH terminus of p185HER-2.…”

Section: Methodsmentioning

confidence: 99%

p95HER-2 Predicts Worse Outcome in Patients with HER-2-Positive Breast Cancer

Sáez

Molina

Ramsey³

et al. 2006

Clinical Cancer Research

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186

125

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Background:The HER-2 receptor undergoes a proteolytic cleavage generating an NH 2 -terminally truncated fragment, p95HER-2, that is membrane-associated and tyrosine-phosphorylated.We have reported that p95HER-2, but not the full-length receptor, p185HER-2, correlated with the extent of lymph node involvement in patients with breast cancer and its expression was significantly enhanced in nodal metastatic tissue. These facts suggested an important role for p95HER-2 either as a marker or cause of metastasis and poor outcome in breast cancer. In this work, we have studied the prognostic value of p95HER-2 in breast cancer. Methods: Primary breast tumor tissues (n = 483) were from surgical resections conducted in hospitals in two different countries: the U.S. (n = 334) and Spain (n = 149). HER-2 protein forms, including p185HER-2 and p95HER-2, were examined in extracts of primary breast tumors by Western blot analysis. The levels of the two forms (high or low) were tested for association with other clinicopathologic factors and for correlation with disease-free survival. Results:The median follow-up was 46 months. A high level of p95HER-2 in primary tumor tissue correlated with reduced 5-year disease-free survival (hazard ratio, 2.55; 95% confidence interval, 2.13-8.01; P < 0.0001). The median time for disease-free survival was 32 versus 139 months in patients with low levels of p95HER-2. In comparison, high levels of the full-length p185HER-2 did not significantly correlate with poor outcome (P > 0.1). Multivariate analysis revealed that high p95HER-2 was an independent predictor of disease-free survival (hazard ratio, 1.59; 95% confidence interval, 1.246-1.990; P = 0.0004). Conclusions: p95HER-2 expression is an independent prognostic factor in breast cancer and defines a group of patients with HER-2-positive breast cancer with significantly worse outcome.

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“…Immunoprecipitation of the EGF receptor was performed as described (Lin et al, 1990). Briefly, normal HMECs grown in the absence of EGF and A431 cells grown in DMEM plus 5% serum were collected and lysed in TG buffer (50 mM HEPES, pH 7.4, 1% Triton X-100, 10% glycerol, 1% Aprotinin) for 5 min.…”

Section: Immunoprecipitationmentioning

confidence: 99%

Heparin inhibition of autonomous growth implicates amphiregulin as an autocrine growth factor for normal human mammary epithelial cells

Plowman

Buckley

et al. 1992

Journal Cellular Physiology

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Normal human mammary epithelial cells (HMECs) proliferate in a serum-free defined growth medium in the absence of epidermal growth factor (Li and Shipley, 1991). Amphiregulin (AR) is a heparin-regulated, EGF-like growth factor. Our observation that one strain of HMECs produce AR mRNA (Cook et al., 1991 a) stimulated us to determine whether AR expression was a common phenomenon in HMECs and whether AR could act as an autocrine growth factor to support the EGF-independent growth of these cells. In this study, we detected high levels of AR expression in four separate HMEC strains while one immortal mammary cell line (HBL-100) and six mammary tumor-derived cell lines had low to undetectable levels of AR. The EGF-independent growth of HMECs was blocked by the addition of heparin or a monoclonal anti-EGF receptor antibody to the culture medium, implicating AR as an autocrine growth mediator. This hypothesis is further supported by the fact that medium conditioned by HMECs contains secreted AR protein. A mammary tumor-derived cell line, Hs578T, which proliferates in an EGF-independent manner, does not express detectable levels of AR and is not growth inhibited by heparin. Examination of the same cell types for expression of transforming growth factor type-alpha (TGF-alpha) mRNA revealed coordinate expression of AR and TGF-alpha in these cells. These data suggest that both AR and TGF-alpha mRNA are produced in much greater abundance by normal HMECs than in tumor-derived cells in culture, and that AR is an important autostimulatory factor for the growth of normal HMECs.

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Insulin and epidermal growth factor stimulate phosphorylation of p185HER-2 in the breast carcinoma cell line, BT474

Cited by 13 publications

References 27 publications

Mechanisms of Tamoxifen Resistance: Increased Estrogen Receptor-HER2/neu Cross-Talk in ER/HER2-Positive Breast Cancer

Mechanisms of Tamoxifen Resistance: Increased Estrogen Receptor-HER2/neu Cross-Talk in ER/HER2-Positive Breast Cancer

p95HER-2 Predicts Worse Outcome in Patients with HER-2-Positive Breast Cancer

Heparin inhibition of autonomous growth implicates amphiregulin as an autocrine growth factor for normal human mammary epithelial cells

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