Oshima, Robert G., Lesperance, Jacqueline, Munoz, Varinia, Hebbard, Lionel, Ranscht, Barbara, Sharan, Niki, Muller, William J., Hauser, Craig A., and Cardiff, Robert D. (2004) Angiogenic acceleration of Neu induced mammary tumor progression and metastasis. Cancer research, 64. pp. 169-179.

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Abstract

The Neu (ErbB2, HER2) member of the epidermal growth factor receptor family is implicated in many human breast cancers. We have tested the importance of increased angiogenic signaling in the NeuYD [mouse mammary tumor virus (MMTV)-Neu(ndl)-YD5] mammary tumor model. Transgenic mice expressing vascular endothelial growth factor (VEGF)(164) from the MMTV promoter were generated. These mice expressed VEGF(164) RNA and protein at 20- to 40-fold higher levels throughout mammary gland development but exhibited normal mammary gland development and function. However, in combination with the NeuYD oncogene, VEGF(164) expression resulted in increased vascularization of hyperplastic mammary epithelium and dramatic acceleration of tumor appearance from 111 to 51 days. Gene expression profiling also indicated that the VEGF-accelerated tumors were substantially more vascularized and less hypoxic. The preferential vascularization of early hyperplastic portions of mammary epithelia in NeuYD;MMTV-VEGF animals was associated with NeuYD RNA expression, disorganization of the tight junctions, and overlapping transgenic VEGF expression. NeuYD;MMTV-VEGF(164) bigenic, tumor-bearing animals resulted in an average of 10 tumor cell colonies/lung lodged within vascular spaces. No similar lung colonies were found in control NeuYD mice with similar tumor burdens. Overall, these results demonstrate the angiogenic restriction of early hyperplastic mammary lesions. They also reinforce in vivo the importance of activated Neu in causing disorganization of mammary luminal epithelial cell junctions and provide support for an invasion-independent mechanism of metastasis.

Item ID:	40168
Item Type:	Article (Research - C1)
ISSN:	1538-7445
Funders:	California Breast Cancer Research Program (CBCRP), Department of Defense Breast Cancer Research Program (DOD), National Cancer Institute (NCI), Canadian Breast Cancer Initiative, National Institute of Child Health and Human Development (NICHHD), Cancer Center Support (CCS)
Projects and Grants:	CBCRP 6JB-0073, DOD DAMD-17-00-0175, NCI CA 74597, NICHHD HD 25938, CCS CA 30199
Date Deposited:	31 Aug 2015 01:57
FoR Codes:	11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology @ 100%
SEO Codes:	92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
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