scholarly journals Incomplete surgical resection of ductal carcinomas in situ results in activation of ERBB2 in residual breast cancer cells

2009 ◽  
Vol 16 (1) ◽  
pp. 73-83 ◽  
Author(s):  
Christian F Singer ◽  
Gernot Hudelist ◽  
Eva-Maria Fuchs ◽  
Wolfgang Köstler ◽  
Anneliese Fink-Retter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Receptor Activation ◽  
Incomplete Resection ◽  
Erbb2 Protein ◽  
Ductal Carcinomas

ERBB2 amplification and consecutive overexpression is a predictor for poor prognosis in breast cancer patients. In addition, incomplete resection of ERBB2-overexpressing tumors leads to increased proliferation of residual breast cancer cells. While the local release of cytokines is thought to be responsible for the malignant behavior of remaining tumor tissue, the exact mechanism is still unknown. We have analyzed epidermal growth factor receptor (EGFR), activated (p)EGFR, and activated (p)ERBB2 protein expression in ERBB2-overexpressing and in non-ERBB2-overexpressing tumors from patients who underwent breast surgery and consecutive re-excision for involved margins, and compared expression levels by immunohistochemistry. While overall ERBB2 protein expression in the initial and the re-excised sample were comparable, we observed an increase in pERBB2 in ductal carcinomas in situ in both, ERBB2-overexpressing (16/21 vs 24/24; P=0.018, χ2 test) and non-ERBB2-overexpressing tumors (3/28 vs 5/12; P=0.025, χ2 test). pERBB2 was not increased in invasive tumors, regardless on whether the samples had been taken from a ERBB2-overexpressing (9/25 vs 6/17; P=0.261, χ2 test) or a non-ERBB2-overexpressing tumor (1/27 vs 0/8; P=0.581, χ2 test). EGFR expression was only detected in 1/47 ERBB2-overexpressing primary tumors and 2/48 non-ERBB2-overexpressing tumors, and was undetectable in re-excised specimen. Taken together, we have demonstrated an increase in ERBB2 receptor activation in incompletely resected preinvasive breast cancer. We hypothesize that receptor phosphorylation is caused by growth factor stimulation in response to intraoperative tissue damage, and perioperative inhibition of specific cytokines could become a promising therapeutic strategy.

Incomplete surgical resection of DCIS results in activation of HER-2 in residual breast cancer cells

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22035-e22035
Author(s):  
C. F. Singer ◽  
G. Hudelist ◽  
E. Fuchs ◽  
W. Köstler ◽  
A. Fink-Retter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Receptor Activation ◽  
Incomplete Resection ◽  
Chi Square ◽  
Her2 Protein ◽  
Chi Square Test ◽  
Her 2

e22035 Background: HER-2 amplification and consecutive overexpression is a predictor for poor prognosis in breast cancer patients. In addition, incomplete resection of HER2 overexpressing tumors leads to increased proliferation of residual breast cancer cells. While the local release of cytokines is thought to be responsible for the malignant behaviour of remaining tumor tissue, the exact mechanism is still unknown. Methods: We have analyzed EGFR, activated (p)EGFR, and activated (p)HER2 protein expression in HER2 overexpressing and in non-HER2 overexpressing tumors from patients who underwent breast surgery and consecutive reexcision for involved margins, and compared expression levels by IHC. Results: While overall HER2 protein expression in the initial and the reexcised sample were comparable, we observed an increase in pHER2 in DCIS in both, HER2 overexpressing (16/21 vs 24/24; p=0.018, Chi Square test) and non-HER2 overexpressing tumors (3/28 vs 5/12; p=0.025, Chi Square test). pHER2 was not increased in invasive tumors, regardless on whether the samples had been taken from a HER2 overexpressing (9/25 vs 6/17; p=0.261, Chi Square test), or a non-HER2 overexpressing tumor (1/27 vs 0/8; p=0.581, Chi Square test). EGFR expression was only detected in 1/47 HER2 overexpressing primary tumors and 2/48 non-HER2 overexpressing tumors, and was undetectable in reexcised specimen. Conclusions: Taken together, we have demonstrated an increase in HER2 receptor activation in incompletely resected preinvasive breast cancer. We hypothesize that receptor phosphorylation is caused by growth factor stimulation in response to intraoperative tissue damage, and perioperative inhibition of specific cytokines could become a promising therapeutic strategy. No significant financial relationships to disclose.

scholarly journals All trans-retinoic acid acts synergistically with hydroxytamoxifen and transforming-growth factor β to stimulate apoptosis in MCF-7 breast cancer cells

2004 ◽  
Vol 183 (2) ◽  
pp. 395-404 ◽  
Author(s):  
D N Danforth
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Transforming Growth Factor ◽  
Synergistic Effects ◽  
Transforming Growth Factor Β ◽  
Mcf 7

The anti-estrogen 4-hydroxytamoxifen (TAM) and vitamin A-related compounds, the retinoids, in combination act synergistically to inhibit growth of breast cancer cells in vitro and in vivo. To clarify the mechanism of this synergism, the effect of TAM and all trans-retinoic acid (AT) on proliferation of MCF-7 breast cancer cells was studied in vitro. TAM and AT acted synergistically to cause a time-dependent and dose-dependent inhibition of MCF-7 cell growth. In a temporally related manner, TAM+AT acted synergistically to downregulate Bcl-2 mRNA and Bcl-2 protein expression, and to stimulate apoptosis. TAM and AT each blocked cell cycle progression throughout 7 days of treatment but without any synergistic or additive effect on this process, indicating a selective synergism for apoptosis. The negative growth factor-transforming growth factor β (TGFβ) is secreted by these cells and was studied as a potential mediator of the synergistic effects of TAM+AT on apoptosis. TAM+AT acted synergistically to induce a fivefold increase in TGFβ1 secretion over 72 h. TGFβ1 alone had no apoptotic effects on these cells; however, TGFβ1 in combination with AT acted synergistically to inhibit growth, to downregulate Bcl-2 mRNA and Bcl-2 protein expression, and to stimulate apoptosis of these cells in a manner comparable with that noted for TAM+AT. The synergism of both TAM+AT and TGFβ1+AT for apoptosis was suppressed by estradiol. Co-incubation of TAM+AT with anti-TGFβ antibody did not block down-regulation of Bcl-2 protein expression or stimulation of apoptosis. The synergistic effects of TAM+AT on apoptosis therefore occur independently of TGFβ, although TGFβ may interact with AT in a novel manner to provide another important anti-proliferative mechanism for breast cancer cells.

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