TY - JOUR
T1 - The role of HER2 in angiogenesis
AU - Kumar, Rakesh
AU - Yarmand-Bagheri, Rozita
N1 - Funding Information:
From the Department of Mokcular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX. Supported by the National Institutes of Health grants CA65746 and CA80066 and the Breast and Ovarian Research Programs of The Uniwrsity of Texas M. D. Am&son Cancer Center (RK) Address reprint requests to Rakesh Kumar, PhD, The University of Texas M. D. Anderson Cancer Center, Box 108, 1515 HOC combe Bbd, Houston, 7-X 77030. Copyright 0 2001 by W.B. Saunders Company 0093-7754/01/2805-1605$35.00/O doi:i0.1053/sonc.2001.28547
PY - 2001
Y1 - 2001
N2 - Recent studies have established that growth factors and their receptors play an essential role in regulating the proliferation of epithelial cells. Abnormalities in the expression, structure, or activity of their proto-oncogene products contribute to the development and maintenance of the malignant phenotype. For example, c-erbB2 encodes the human epidermal growth factor receptor 2 (HER2), which is overexpressed or amplified or both in several human malignancies including breast, ovarian, and colon cancers. Tumor cells must use the process of vascularization (angiogenesis) for productive growth and metastasis. Overexpression of HER2 in human tumor cells is closely associated with increased angiogenesis and expression of vascular endothelial growth factor (VEGF). Indeed, when the VEGF pathway is inhibited, tumor growth is suppressed. The anti-HER2 blocking antibody trastuzumab has been shown to inhibit tumor cell growth and VEGF expression. Cancer cell invasiveness can be promoted, even in the absence of HER2 overexpression, by transregulation of HER2 by heregulins that bind to HER3 and HER4. Accordingly, heregulin ΒI regulates the expression and secretion of VEGF in breast cancer cells, and trastuzumab inhibits heregulinmediated angiogenesis both in vitro and in vivo. Thus, potential upregulation of VEGF in cancer epithelial cells likely supports angiogenesis, sustaining and promoting survival and metastasis of tumor cells.
AB - Recent studies have established that growth factors and their receptors play an essential role in regulating the proliferation of epithelial cells. Abnormalities in the expression, structure, or activity of their proto-oncogene products contribute to the development and maintenance of the malignant phenotype. For example, c-erbB2 encodes the human epidermal growth factor receptor 2 (HER2), which is overexpressed or amplified or both in several human malignancies including breast, ovarian, and colon cancers. Tumor cells must use the process of vascularization (angiogenesis) for productive growth and metastasis. Overexpression of HER2 in human tumor cells is closely associated with increased angiogenesis and expression of vascular endothelial growth factor (VEGF). Indeed, when the VEGF pathway is inhibited, tumor growth is suppressed. The anti-HER2 blocking antibody trastuzumab has been shown to inhibit tumor cell growth and VEGF expression. Cancer cell invasiveness can be promoted, even in the absence of HER2 overexpression, by transregulation of HER2 by heregulins that bind to HER3 and HER4. Accordingly, heregulin ΒI regulates the expression and secretion of VEGF in breast cancer cells, and trastuzumab inhibits heregulinmediated angiogenesis both in vitro and in vivo. Thus, potential upregulation of VEGF in cancer epithelial cells likely supports angiogenesis, sustaining and promoting survival and metastasis of tumor cells.
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U2 - 10.1053/sonc.2001.28547
DO - 10.1053/sonc.2001.28547
M3 - Article
C2 - 11706393
AN - SCOPUS:0035174126
SN - 0093-7754
VL - 28
SP - 27
EP - 32
JO - Seminars in oncology
JF - Seminars in oncology
IS - 5 SUPPL. 16
ER -