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Title: Cyr61 promotes breast tumorigenesis and cancer progression

Abstract

Cyr61, a member of the CCN family of genes, is an angiogenic factor. We have shown that it is overexpressed in invasive and metastatic human breast cancer cells and tissues. Here, we investigated whether Cyr61 is necessary and/or sufficient to bypass the ''normal'' estrogen (E2) requirements for breast cancer cell growth. Our results demonstrate that under E2-depleted condition, Cyr61 is sufficient to induce MCF-7 cells grow in the absence of E2. MCF-7 cells transfected with Cyr61 (MCF-7/Cyr61) became E2-independent but still E2-responsive. On the other hand, MCF-7/vector cells remain E2-dependent. MCF-7/Cyr61 cells acquire an antiestrogen-resistant phenotype, one of the most common clinical occurrences during breast cancer progression. MCF-7/Cyr61 cells are anchorage-independent and capable of forming Matrigel outgrowth patterns in the absence of E2. ERa expression in MCF-7/Cyr61 cells is decreased although still functional. Additionally, MCF-7/Cyr61 cells are tumorigenic in ovariectomized athymic nude mice. The tumors resemble human invasive carcinomas with increased vascularization and overexpression of vascular endothelial growth factor (VEGF). Our results demonstrate that Cyr61 is a tumor-promoting factor and a key regulator of breast cancer progression. This study provides evidence that Cyr61 is sufficient to induce E2-independence and anti-E2 resistance, and to promote invasiveness in vitro, and to inducemore » tumorigenesis in vivo, all of which are characteristics of an aggressive breast cancer phenotype.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE; National Institutes of Health Contract DK49049, Department of Defense Breast Cancer Research Program Postdoctoral Traineeship (US)
OSTI Identifier:
837722
Report Number(s):
LBNL-49521
R&D Project: 447401; TRN: US200506%%353
DOE Contract Number:
AC03-76SF00098
Resource Type:
Journal Article
Resource Relation:
Journal Name: Oncogene; Journal Volume: 21; Journal Issue: 53; Other Information: Submitted to Oncogene: Volume 21, No.53; Journal Publication Date: 11/21/2002; PBD: 16 Jan 2002
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CARCINOMAS; ESTROGENS; GENES; GROWTH FACTORS; IN VITRO; IN VIVO; MAMMARY GLANDS; MICE; NEOPLASMS; PHENOTYPE

Citation Formats

Tsai, Miaw-Sheue, Bogart, Daphne F., Castaneda, Jessica M., Li, Patricia, and Lupu, Ruth. Cyr61 promotes breast tumorigenesis and cancer progression. United States: N. p., 2002. Web. doi:10.1038/sj.onc.1205682.
Tsai, Miaw-Sheue, Bogart, Daphne F., Castaneda, Jessica M., Li, Patricia, & Lupu, Ruth. Cyr61 promotes breast tumorigenesis and cancer progression. United States. doi:10.1038/sj.onc.1205682.
Tsai, Miaw-Sheue, Bogart, Daphne F., Castaneda, Jessica M., Li, Patricia, and Lupu, Ruth. Wed . "Cyr61 promotes breast tumorigenesis and cancer progression". United States. doi:10.1038/sj.onc.1205682. https://www.osti.gov/servlets/purl/837722.
@article{osti_837722,
title = {Cyr61 promotes breast tumorigenesis and cancer progression},
author = {Tsai, Miaw-Sheue and Bogart, Daphne F. and Castaneda, Jessica M. and Li, Patricia and Lupu, Ruth},
abstractNote = {Cyr61, a member of the CCN family of genes, is an angiogenic factor. We have shown that it is overexpressed in invasive and metastatic human breast cancer cells and tissues. Here, we investigated whether Cyr61 is necessary and/or sufficient to bypass the ''normal'' estrogen (E2) requirements for breast cancer cell growth. Our results demonstrate that under E2-depleted condition, Cyr61 is sufficient to induce MCF-7 cells grow in the absence of E2. MCF-7 cells transfected with Cyr61 (MCF-7/Cyr61) became E2-independent but still E2-responsive. On the other hand, MCF-7/vector cells remain E2-dependent. MCF-7/Cyr61 cells acquire an antiestrogen-resistant phenotype, one of the most common clinical occurrences during breast cancer progression. MCF-7/Cyr61 cells are anchorage-independent and capable of forming Matrigel outgrowth patterns in the absence of E2. ERa expression in MCF-7/Cyr61 cells is decreased although still functional. Additionally, MCF-7/Cyr61 cells are tumorigenic in ovariectomized athymic nude mice. The tumors resemble human invasive carcinomas with increased vascularization and overexpression of vascular endothelial growth factor (VEGF). Our results demonstrate that Cyr61 is a tumor-promoting factor and a key regulator of breast cancer progression. This study provides evidence that Cyr61 is sufficient to induce E2-independence and anti-E2 resistance, and to promote invasiveness in vitro, and to induce tumorigenesis in vivo, all of which are characteristics of an aggressive breast cancer phenotype.},
doi = {10.1038/sj.onc.1205682},
journal = {Oncogene},
number = 53,
volume = 21,
place = {United States},
year = {Wed Jan 16 00:00:00 EST 2002},
month = {Wed Jan 16 00:00:00 EST 2002}
}