Gastrin-Releasing Peptide Receptor in Breast Cancer Mediates Cellular Migration and Interleukin-8 Expression

• Published in: The Journal of surgical research 2009-09, Vol.156 (1), p.26-31
• Main Authors: Chao, Celia, M.D, Ives, Kirk, B.S, Hellmich, Helen L., Ph.D, Townsend, Courtney M., M.D, Hellmich, Mark R., Ph.D
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; bombesin; Bombesin - pharmacology; breast cancer; Breast Neoplasms - metabolism; Cell Line, Tumor; Cell Movement; Cell Proliferation - drug effects; Drug Synergism; Epidermal Growth Factor - pharmacology; Female; gastrin-releasing peptide receptor; General aspects; Gynecology. Andrology. Obstetrics; Humans; interleukin-8; Interleukin-8 - metabolism; Mammary gland diseases; Medical sciences; migration; Neurotransmitter Agents - pharmacology; Receptor, Epidermal Growth Factor - metabolism; Receptors, Bombesin - metabolism; RNA, Messenger - metabolism; Surgery; Tumors; Up-Regulation - drug effects
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2009.03.072

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.