TY - JOUR
T1 - Gastrin-Releasing Peptide Receptor in Breast Cancer Mediates Cellular Migration and Interleukin-8 Expression
AU - Chao, Celia
AU - Ives, Kirk
AU - Hellmich, Helen L.
AU - Townsend, Courtney M.
AU - Hellmich, Mark R.
N1 - Funding Information:
The authors thank Dr. Javier Navarro for the plasmids containing the IL-8 cDNA, and Eileen Figueroa and Steve Schuenke for assistance with the preparation of this manuscript. CC is supported by a research career development award (K12HD052023: Building Interdisciplinary Research Careers in Women's Health Program-BIRCWH) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); the National Institute of Allergy and Infectious Diseases (NIAID); and the Office of the Director (OD), National Institutes of Health. The content is solely the responsibility of the authors and does not represent the official views of these Institutes or the National Institutes of Health.
PY - 2009/9
Y1 - 2009/9
N2 - Background: Breast cancers aberrantly express gastrin-releasing peptide (GRP) hormone and its cognate receptor, gastrin-releasing peptide receptor (GRP-R). Experimental evidence suggests that bombesin (BBS), the pharmacological homologue of GRP, promotes breast cancer growth and progression. The contribution of GRP-R to other poor prognostic indicators in breast cancer, such as the expression of the EGF-R family of growth factors and hormone insensitivity, is unknown. Materials and Methods: Two estrogen receptor (ER)-negative breast cancer cell lines were used. MDA-MB-231 overexpress both EGFR and GRPR, whereas SK-BR-3 cells express EGF-R but lack GRP-R. Cellular proliferation was assessed by Coulter counter. Chemotactic migration was performed using Transwell chambers, and the migrated cells were quantified. Northern blot and real-time PCR were used to evaluate proangiogenic factor interleukin-8 (IL-8) mRNA expression. Results: In MDA-MB-231 cells, GRP-R and EGF-R synergize to regulate cell migration, IL-8 expression, but not cell proliferation. In SK-BR-3 cells, ectopic expression of GRP-R was sufficient to increase migration and IL-8 mRNA. Conclusions: These data suggest relevant roles for GRP-R in ER-negative breast cancer progression. Future mechanistic studies to define the molecular role of GRP-R in breast cancer metastasis provide novel targets for the treatment of ER-negative breast cancers.
AB - Background: Breast cancers aberrantly express gastrin-releasing peptide (GRP) hormone and its cognate receptor, gastrin-releasing peptide receptor (GRP-R). Experimental evidence suggests that bombesin (BBS), the pharmacological homologue of GRP, promotes breast cancer growth and progression. The contribution of GRP-R to other poor prognostic indicators in breast cancer, such as the expression of the EGF-R family of growth factors and hormone insensitivity, is unknown. Materials and Methods: Two estrogen receptor (ER)-negative breast cancer cell lines were used. MDA-MB-231 overexpress both EGFR and GRPR, whereas SK-BR-3 cells express EGF-R but lack GRP-R. Cellular proliferation was assessed by Coulter counter. Chemotactic migration was performed using Transwell chambers, and the migrated cells were quantified. Northern blot and real-time PCR were used to evaluate proangiogenic factor interleukin-8 (IL-8) mRNA expression. Results: In MDA-MB-231 cells, GRP-R and EGF-R synergize to regulate cell migration, IL-8 expression, but not cell proliferation. In SK-BR-3 cells, ectopic expression of GRP-R was sufficient to increase migration and IL-8 mRNA. Conclusions: These data suggest relevant roles for GRP-R in ER-negative breast cancer progression. Future mechanistic studies to define the molecular role of GRP-R in breast cancer metastasis provide novel targets for the treatment of ER-negative breast cancers.
KW - bombesin
KW - breast cancer
KW - gastrin-releasing peptide receptor
KW - interleukin-8
KW - migration
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U2 - 10.1016/j.jss.2009.03.072
DO - 10.1016/j.jss.2009.03.072
M3 - Article
C2 - 19631337
AN - SCOPUS:68649095592
SN - 0022-4804
VL - 156
SP - 26
EP - 31
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -