Tyrosine Kinase, p56 -induced Cell Motility, and Urokinase-type Plasminogen Activator Secretion Involve Activation of Epidermal Growth Factor Receptor/Extracellular Signal Regulated Kinase Pathways

Mahabeleshwar, Ganapati H.; Das, Riku; Kundu, Gopal C.

doi:10.1074/jbc.m311400200

Cited by 23 publications

(23 citation statements)

References 27 publications

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“…The morphological changes generated by EGF in MCF-7 cells correlated with an increase in cell motility. Although, this result is support by the reports that associated EGFR activation with cell motility, [35][36][37][38] we demonstrated that EGFR activation by itself, in the absence of other growth factors, can induce motility in MCF-7 cells.…”

Section: Discussionsupporting

confidence: 61%

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EGF Induces Cell Motility and Multi-Drug Resistance Gene Expression in Breast Cancer Cells

García¹,

Franklin²,

McCubrey³

2006

Cell Cycle

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The epidermal growth factor receptor (EGFR) is important for normal development, differentiation, and cell proliferation. Deregulation of EGFR has been observed in breast cancer. EGFR and signal pathways activated by these receptors have been associated with an advanced tumor stage and a poor clinical prognosis in breast cancer; however, the precise mechanisms responsible for this process are still not known. Here we show that treatment of MCF-7 breast cancer cells with EGF activated Akt and ERK, induced morphological changes, and increased cell motility. In addition, the constitutive expression of Raf-1 and the use of a MEK inhibitor demonstrated the participation of the Raf/MEK/ERK pathway in these processes. Importantly we detected that EGF induced MRP-1, 3, 5 and 7 gene expression and an increase in MRP1 promoter activity. In conclusion, treatment of MCF-7 breast cancer cells with EGF, in the absence of other growth factors, resulted in activation of EGFR signal transduction pathways; which were related with cell motility and drug resistance.

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Section: Discussionsupporting

confidence: 61%

“…Activation of the EGFR signaling pathway has been associated with multidrug resistance. [37][38][39][40][41][42] We demonstrated whether EGFR activation by itself could be involved in this process. MCF-7 cells were treated with EGF for 96 hours and the expression of genes involved with drug resistance were analyzed by RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

EGF Induces Cell Motility and Multi-Drug Resistance Gene Expression in Breast Cancer Cells

García¹,

Franklin²,

McCubrey³

2006

Cell Cycle

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“…There are two types of endogenous OPN receptors. One has been reported to be CD44 (Weber et al, 1996), which forms a complex with srcrelated kinases (Rozsnyay, 1999) to induce MAPK (Mahabeleshwar et al, 2004). Alternatively, OPN may interact with intergrin a v b 1 , a v b 3 or a v b 5 (Hu et al, 1995), where b 1 -containing integrins have been associated with MAPK activation (Berken et al, 2003).…”

Section: H-rasv12 and Opn Synergistically Activate Mapk And Induce Fomentioning

confidence: 99%

Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and transformation by H-RasV12

Teramoto

Castellone

Malek³

et al. 2004

Oncogene

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Activated forms of Ras family members are prevalent in many cancers where Ras mutants transduce signals essential for transformation, angiogenesis, invasion and metastasis. As a cancer progression model, we used NIH3T3 cells to explore the mechanism of Ras-induced tumorigenesis. Ras family mutants H-RasV12 and Rit79L strongly induced foci formation, while Rho family mutants RhoA-QL, Rac1-QL and Cdc42-QL were less effective. A comparison of downstream transcriptional targets of Ras and Rho family members using a 26 383 element cDNA microarray revealed that the osteopontin (OPN) gene exhibited the best correlation between magnitude of gene expression change and level of foci formation (r ¼ 0.96, Po0.001). In association with H-RasV12-and Rit79L-mediated transformation, foci secreted OPN protein and upregulated the OPN receptor CD44, suggesting the novel initiation of an aberrant OPN-CD44-Rac autocrine pathway. In support of this were the following observations. First, RGD-deficient OPN protein-binding activity was present in H-RasV12-transformed cells but not in control cells, and binding activity was inhibited by the CD44 blocking antibody. Second, foci formation, cell invasion and Rac activity were induced by H-RasV12 and inhibited by the CD44 blocking antibody. Third, foci formation by H-RasV12 was substantially reduced by a short interfering RNA (siRNA) specifically targeting OPN expression for knockdown. Fourth, H-RasV12-mediated transformation was not blocked by the GRGDS peptide, suggesting that OPN effects were not mediated by the integrins. Lastly, OPN knockdown affected the downstream expression of 160 '2nd tier' genes, and at least a subset of these genes appears to be involved in transformation. Indeed, four genes were selected for knockdown, each resulting in a disruption of foci formation and/or invasion. These results underscore the role of aberrant autocrine signaling and transcriptional networking during tumorigenesis.

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“…Multiple signal transduction pathways, including Src, Ras, Raf, mitogen-activated protein kinase (MAPK) kinase, c-Jun NH 2 -terminal kinase, and protein kinase C pathways, are involved in EGF-EGFR-induced transcriptional activations of various genes during physiologic and pathophysiologic needs (23,(29)(30)(31)(32). Moreover, estrogen, through its membrane receptor, rapidly activates several downstream signaling cascades that may eventually trigger the cross-talk between ER and EGFR, which in turn leads to activation of several signal transduction pathways and genes required to alter the cell biology of breast cancer (23,33).…”

Section: Involvement Of Signal Transduction Pathways In Egfinduced Wimentioning

confidence: 99%

Epidermal Growth Factor Induces WISP-2/CCN5 Expression in Estrogen Receptor-α-Positive Breast Tumor Cells through Multiple Molecular Cross-talks

Banerjee

Sengupta²,

Saxena³

et al. 2005

Molecular Cancer Research

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Epidermal growth factor (EGF) is a mitogen for estrogen receptor (ER) -positive breast tumor cells, and it has been proven that EGF occasionally mimicked estrogen action and cross-talks with ER-A to exert its activity. Therefore, the present study was undertaken to explore whether EGF is able to modulate the expression of Wnt-1-induced signaling protein-2/connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed 5 (WISP-2/CCN5), an estrogenresponsive gene, in normal and transformed cell lines of the human breast and, if so, whether this induction is critical for EGF mitogenesis and what downstream signaling pathways are associated with this event. Here, we show that EGF-induced WISP-2 expression in ER-and EGF receptor -positive noninvasive MCF-7 breast tumor cells was dose and time dependent and that expression was modulated at transcription level. A synergism was seen in combination with estrogen. Moreover, small interfering RNA -mediated inhibition of WISP-2/CCN5 activity in MCF-7 cells resulted in abrogation of proliferation by EGF. The multiple molecular cross-talks, including the interactions between phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase signaling pathways and two diverse receptors (i.e., ER-A and EGFR), were essential in the event of EGF-induced WISP-2/CCN5 up-regulation in MCF-7 cells. Moreover, EGF action on WISP-2/CCN5 is restricted to ER-and EGFR-positive noninvasive breast tumor cells, and this

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Tyrosine Kinase, p56 -induced Cell Motility, and Urokinase-type Plasminogen Activator Secretion Involve Activation of Epidermal Growth Factor Receptor/Extracellular Signal Regulated Kinase Pathways

Abstract: We have recently reported that tyrosine kinase, p56 lck and EGF receptor in these processes in breast cancer cells is not well defined. We provide here evidence that H/R

Cited by 23 publications

References 27 publications

EGF Induces Cell Motility and Multi-Drug Resistance Gene Expression in Breast Cancer Cells

EGF Induces Cell Motility and Multi-Drug Resistance Gene Expression in Breast Cancer Cells

Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and transformation by H-RasV12

Epidermal Growth Factor Induces WISP-2/CCN5 Expression in Estrogen Receptor-α-Positive Breast Tumor Cells through Multiple Molecular Cross-talks

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