Gastrin-releasing peptide receptor in breast cancer mediates cellular migration and interleukin-8 expression.
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.


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.
Chao
Celia
C
Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USA.
Ives
Kirk
K
Hellmich
Helen L
HL
Townsend
Courtney M
CM
Hellmich
Mark R
MR
D001839:Bombesin / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018004:Receptors, Bombesin / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D016209:Interleukin-8; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D018004:Receptors, Bombesin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D001839:Bombesin