Bradykinin stimulates cell proliferation through an extracellular-regulated kinase 1 and 2-dependent mechanism in breast cancer cells in primary culture.
We have previously reported that bradykinin (BK) represents an influential mitogenic agent in normal breast glandular tissue. We here investigated the mitogenic effects and the signalling pathways of BK in primary cultured human epithelial breast cells obtained from a tumour and from the histologically proven non-malignant tissue adjacent to the tumour. BK provoked cell proliferation, increase in cytosolic calcium, activation of protein kinase C (PKC)-alpha, -beta, -delta, -epsilon and -eta and phosphorylation of the extracellular-regulated kinases 1 and 2 (ERK1/2). The following compounds blocked the proliferative effects of BK: Hyp3-BK, a B2 receptor subtype inhibitor; U73122, a phospholipase C-beta inhibitor; GF109203X, a protein kinase C (PKC) inhibitor; and PD98059, a mitogen-activated protein kinase kinase inhibitor. Gö6976, a Ca(2+)-dependent PKC inhibitor, did not have any effect. In conclusion, the mitogenic effects of BK are retained in peritumour and tumour cells; hence, it is likely that BK has an important role in cancer endorsement and progression.
Greco
S
S
Department of Biological and Environmental Sciences and Technologies, Ecotekne, Università di Lecce, Monteroni, Via Provinciale per Monteroni, 73100 Lecce, Italy.
Elia
M G
MG
Muscella
A
A
Romano
S
S
Storelli
C
C
Marsigliante
S
S
D000704:Analysis of Variance; D001920:Bradykinin / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000032:analysis; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007424:Intracellular Fluid / Q000737:chemistry; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018002:Receptors, Bradykinin / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D008934:Mitogens; D018002:Receptors, Bradykinin; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D001920:Bradykinin; D002118:Calcium