Bradykinin stimulates cell proliferation through an extracellular-regulated kinase 1 and 2-dependent mechanism in breast cancer cells in primary culture

Abstract

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)-, -, -, -´and -and phosphorylation of the extracellular-regulated kinases 1 and 2 (ERK1/2). The following compounds blocked the proliferative effects of BK: Hyp3-BK, a B 2 receptor subtype inhibitor; U73122, a phospholipase C-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.

Cross-talk between G Protein–Coupled Receptor and Epidermal Growth Factor Receptor Signaling Pathways Contributes to Growth and Invasion of Head and Neck Squamous Cell Carcinoma

“…PGE2 and BK have been implicated in the growth of colon and breast carcinoma, respectively (7,8). Here, we have shown that GPCR ligands PGE2 and BK induce mitogenic effects in HNSCC cells.…”

“…4,6). GPCR ligands prostaglandin E2 (PGE2) and bradykinin (BK) are inflammatory molecules that have been previously reported to contribute to the proliferation of colon and breast cancer cells, respectively (7,8). PGE2 has been reported to activate EGFR in tumors, including colon cancer, by activating other molecules, including Src and matrix metalloproteinases (MMP; refs.…”

Integrative Analysis of Microarray Data with Gene Ontology to Select Perturbed Molecular Functions using Gene Ontology Functional Code

“…There Table 5 Phosphoric ester hydrolase activity CTDSPL2, CTDSPL, PON2, PFKFB1, PFKFB2, IMPA2, INPP5B, NT5C1B, NT5E, DLG7, CTDP1, CILP, PPAP2B, PPAP2C, DLG1, LCK, PPM1A, PPM1H, RGS12, TIAM1, BAG4, MS4A1, DCLK1, BRAF, STYX Table 5 that are implicated to play roles in the progression of breast cancer or other cancers, including BDKRB2 (Greco et al, 2005), PLCB1 (Naor, 2009), PLD1 (Eisen and Brown, 2002), GPLD1 (Derevianko et al, 1996;Williams et al, 2001), EXO1 (Naderi et al, 2007), ANG (Campo et al, 2005), ISG20/HEM45 (Pentecost, 1998), AZGP1/ZAG (Hassan et al, 2009), ZKSCAN1 (Pennanen et al, 2009), REXO2 (Flanagan et al, 2009), CTDSPL (Murabito et al, 2007), NT5E (Zhou et al, 2007), DLG1 (Fuja et al, 2004), PPM1A (Lin et al, 2006), TIAM1 (Lane et al, 2008), BAG4 (Yang et al, 2006), BRAF (Hollestelle, et al, 2007), CLDN4 (Kulka et al, 2009), F3/TF (Amirkhosravi et al, 1998), FZD1 (Benhaj et al, 2006), NGFR (Reis-Filho et al, 2006), LEFR , RAC1 , PLXNB1 (Rody et al, 2007), IGHG1 (Kabbage et al, 2008), IGHG3 (Bin Amer et al, 2008), TLR3 (Salaun et al, 2006), FBN1 , DUSP4 (Venter et al, 2005), PTPN3 (Wang et al, 2004), CDKN3/KAP (Lee et al, 2000), and etc.…”

G Protein-Coupled Receptors-Induced Activation of Extracellular Signal-Regulated Protein Kinase (ERK) and Sodium-Proton Exchanger Type 1 (NHE1)

“…The expression of BK receptors has been demonstrated in clinical speciments of adenocarcinoma, squamous carcinoma, lymphoma, hepatoma and carcinoid, and in experimental mouse sarcoma 180 and colon adenocarcinoma 38 (Wu et al, 2002), in small cell and non-small cell carcinomas of the lung (Chee et al, 2008), and in oesophageal squamous cell carcinoma (Dlamini et al, 2005). The mitogenic effects of BK have been reported in primary cultured epithelial breast cancer cells and in MCF-7 breast cancer cell line, where BK stimulated cell proliferation through ERK activation (Greco et al, 2005;Greco et al, 2006). Because there were limited studies on the role of BK in renal cell carcinomas, we have chosen to use A498 cells, a transformed cell line derived from primary undifferentiated kidney carcinoma (Giard et al, 1973), which represents a widely used model for studying of renal carcinomas.…”