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.
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.
Authors: Paula Paulo; Franclim R Ribeiro; Joana Santos; Diana Mesquita; Mafalda Almeida; João D Barros-Silva; Harri Itkonen; Rui Henrique; Carmen Jerónimo; Anita Sveen; Ian G Mills; Rolf I Skotheim; Ragnhild A Lothe; Manuel R Teixeira Journal: Neoplasia Date: 2012-07 Impact factor: 5.715
Authors: Said M Elshafae; Bardes B Hassan; Wachiraphan Supsavhad; Wessel P Dirksen; Rachael Y Camiener; Haiming Ding; Michael F Tweedle; Thomas J Rosol Journal: Prostate Date: 2016-03-04 Impact factor: 4.104
Authors: Daniela B Cornelio; Caroline B DE Farias; Débora S Prusch; Tiago E Heinen; Rafael P Dos Santos; Ana L Abujamra; Gilberto Schwartsmann; Rafael Roesler Journal: Mol Clin Oncol Date: 2012-08-07