Identification of mitogen-activated protein kinase kinase as a chemoresistant pathway in MCF-7 cells by using gene expression microarray

Weldon, Christopher B.; Scandurro, Ali B.; Rolfe, Kevin W.; Clayton, John L.; Elliott, Steven; Butler, Nancy; Melnik, Lilia I.; Alam, Jawed; McLachlan, John A.; Jaffe, Bernard M.; Beckman, Barbara S.; Burow, Matthew E.

doi:10.1067/msy.2002.125389

Cited by 76 publications

(81 citation statements)

References 24 publications

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“…It has been proven that MEK5 functions act through regulation of its downstream kinase ERK5 (Dent et al, 2003). It has been reported that cyclin D1 and MMP-9 are involved in malignancy and carcinomatosis in MEK5 highly activated breast and prostate carcinoma cells (Weldon et al, 2002;Mehta et al, 2003). However, it remains to be elucidated as to how MEK5 participates in the development of breast malignancies and what role MEK5 plays with aberrant Stat3 signaling.…”

Section: Discussionmentioning

confidence: 97%

“…MEK5 level in prostate cancer is markedly higher than that in normal tissue (Mehta et al, 2003). Since MEK5 is highly associated with Stat3 activation in breast carcinoma cells and tissues, combining existing evidences (Weldon et al, 2002;Mehta et al, 2003), MEK5 is, most likely, directly involved in the development of malignancies and tumorgenesis. It may also become a molecular target in the treatment of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…One report showed drug-resistant MCF7 cells appeared to have significantly high level of MEK5. In that report, MEK5 contributed to prevention of cell apoptosis and chemotherapeutic resistance (Weldon et al, 2002). There are reports that demonstrated that MEK5/ERK5 was involved in malignancies and tumorgenesis (Weldon et al, 2002;Mehta et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…In that report, MEK5 contributed to prevention of cell apoptosis and chemotherapeutic resistance (Weldon et al, 2002). There are reports that demonstrated that MEK5/ERK5 was involved in malignancies and tumorgenesis (Weldon et al, 2002;Mehta et al, 2003). Some studies showed that the activation of MEK5/ERK5 signal pathway drove cyclin D1 and MMP-9 expression and contributed to cell carcinogenesis (Mehta et al, 2003;Mulloy et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

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Stat3 upregulates MEK5 expression in human breast cancer cells

2004

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Stat3 upregulates MEK5 expression in human breast cancer cells

2004

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“…Stimulation of the b2AR results in tumor growth inhibition AE Carie and SM Sebti patients as the genetic aberrations (i.e., Ras mutations, EGF-R and ErbB2 over expression) that result in hyperactivation of the Raf-1/Mek-1/Erk1/2 pathway have all been associated with poor prognosis, resistance to therapy and shortened patient life (Slamon et al, 1987;Weldon et al, 2002;Jin et al, 2003). Using b2 stimulation to cause tumor regression by blocking the Raf-1/Mek-1/Erk1/2 pathway is a novel and powerful approach that could have a widespread use in cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

A chemical biology approach identifies a beta-2 adrenergic receptor agonist that causes human tumor regression by blocking the Raf-1/Mek-1/Erk1/2 pathway

Carie

Sebti

2007

Oncogene

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A chemical biology approach identifies a beta 2 adrenergic receptor (b2AR) agonist ARA-211 (Pirbuterol), which causes apoptosis and human tumor regression in animal models. b2AR stimulation of cAMP formation and protein kinase A (PKA) activation leads to Raf-1 (but not B-Raf) kinase inactivation, inhibition of Mek-1 kinase and decreased phospho-extracellular signal-regulated kinase (Erk)1/2 levels. ARA-211 inhibition of the Raf/ Mek/Erk1/2 pathway is mediated by PKA and not exchange protein activated by cAMP (EPAC). ARA-211 is selective and suppresses P-Erk1/2 but not P-JNK, P-p38, P-Akt or P-STAT3 levels. b2AR stimulation results in inhibition of anchorage-dependent and -independent growth, induction of apoptosis in vitro and tumor regression in vivo. b2AR antagonists and constitutively active Mek-1 rescue from the effects of ARA-211, demonstrating that b2AR stimulation and Mek kinase inhibition are required for ARA-211 antitumor activity. Furthermore, suppression of growth occurs only in human tumors where ARA-211 induces cAMP formation and decreases P-Erk1/2 levels. Thus, b2AR stimulation results in significant suppression of malignant transformation in cancers where it blocks the Raf-1/Mek-1/Erk1/2 pathway by a cAMP-dependent activation of PKA but not EPAC.

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ERK5 is a target for gene amplification at 17p11 and promotes cell growth in hepatocellular carcinoma by regulating mitotic entry

Zen

Yasui

Nakajima

et al. 2008

Genes Chromosomes & Cancer

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Using high-density oligonucleotide microarrays, we investigated DNA copy-number aberrations in cell lines derived from hepatocellular carcinomas (HCCs) and detected a novel amplification at 17p11. To identify the target of amplification at 17p11, we defined the extent of the amplicon and examined HCC cell lines for expression of all seven genes in the 750-kb commonly amplified region. Mitogen-activated protein kinase (MAPK) 7, which encodes extracellular-regulated protein kinase (ERK) 5, was overexpressed in cell lines in which the gene was amplified. An increase in MAPK7 copy number was detected in 35 of 66 primary HCC tumors. Downregulation of MAPK7 by small interfering RNA suppressed the growth of SNU449 cells, the HCC cell line with the greatest amplification and overexpression of MAPK7. ERK5, phosphorylated during the G2/M phases of the cell cycle, regulated entry into mitosis in SNU449 cells. In conclusion, our results suggest that MAPK7 is likely the target of 17p11 amplification and that the ERK5 protein product of MAPK7 promotes the growth of HCC cells by regulating mitotic entry.

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Identification of mitogen-activated protein kinase kinase as a chemoresistant pathway in MCF-7 cells by using gene expression microarray

Cited by 76 publications

References 24 publications

Stat3 upregulates MEK5 expression in human breast cancer cells

Stat3 upregulates MEK5 expression in human breast cancer cells

A chemical biology approach identifies a beta-2 adrenergic receptor agonist that causes human tumor regression by blocking the Raf-1/Mek-1/Erk1/2 pathway

ERK5 is a target for gene amplification at 17p11 and promotes cell growth in hepatocellular carcinoma by regulating mitotic entry

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