Regulation of sphingosine kinase 1 gene expression by protein kinase C in a human leukemia cell line, MEG-O1

Nakade, Yusuke; Banno, Yoshiko; T-Koizumi, Keiko; Hagiwara, Kaoru; Sobue, Satoshi; Koda, Masahiro; Suzuki, Motoshi; Kojima, Tetsuhito; Takagi, Akira; Asano, Haruhiko; Nozawa, Yoshinori; Murate, Takashi

doi:10.1016/j.bbalip.2003.11.001

Cited by 58 publications

(52 citation statements)

References 48 publications

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“…Several potential transcription factor binding sites have been identified in the SPHK promoter region, including Sp1, AP1, AP2, AP4 and STAT (Nakade et al 2003, Sobue et al 2005. However, which transcription factors account for the SPHK gene regulation by ER remains to be identified.…”

Section: Figurementioning

confidence: 99%

Role of sphingolipids in oestrogen signalling in breast cancer cells: an update

Sukocheva¹,

Wadham²

2013

Journal of Endocrinology

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The signaling pathways activated by the steroid hormone oestrogen include a variety of cytoplasmic second messengers linked to a multitude of tissue-specific effects. In the last decade, sphingolipids and their membrane receptors were added to the list of oestrogenactivated mediators. Oestrogen triggers the sphingolipid signalling cascade in various tissues including breast cancer. Extensive research has shown that sphingolipids are the key regulatory molecules in growth factor networks. Sphingolipids can control the rate of cell proliferation and the differentiation outcome during malignant transformation. In this study, we summarise novel experimental evidences linking sphingolipids to oestrogenactivated effects, highlight the role of sphingolipids in cancer cells and discuss new avenues for future research at the intersection between oestrogen and sphingolipid signalling.

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Section: Figurementioning

confidence: 99%

Role of sphingolipids in oestrogen signalling in breast cancer cells: an update

Sukocheva¹,

Wadham²

2013

Journal of Endocrinology

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“…The promoter of SK1 contains Sp1 and AP2 transcriptional sites (23). Sp1 is constitutively associated with the SK1 promoter and interacts cooperatively with AP2 that is activated by agents acting via ERK-1/2 (23,33).…”

mentioning

confidence: 99%

Sphingosine Kinase 1 Induces Tolerance to Human Epidermal Growth Factor Receptor 2 and Prevents Formation of a Migratory Phenotype in Response to Sphingosine 1-Phosphate in Estrogen Receptor-Positive Breast Cancer Cells

Long

Edwards

Watson

et al. 2010

Molecular and Cellular Biology

133

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We demonstrate here a new concept termed "oncogene tolerance" whereby human EGF receptor 2 (HER2) increases sphingosine kinase 1 (SK1) expression in estrogen receptor-positive (ER ؉ ) MCF-7 HER2 cells and SK1, in turn, limits HER2 expression in a negative-feedback manner. The HER2-dependent increase in SK1 expression also limits p21-activated protein kinase 1 (p65 PAK1) and extracellular signal regulated kinase 1/2 (ERK-1/2) signaling. Sphingosine 1-phosphate signaling via S1P 3 is also altered in MCF-7 HER2 cells. In this regard, S1P binding to S1P 3 induces a migratory phenotype via an SK1-dependent mechanism in ER ؉ MCF-7 Neo cells, which lack HER2. This involves the S1P stimulated accumulation of phosphorylated ERK-1/2 and actin into membrane ruffles/lamellipodia and migration. In contrast, S1P failed to promote redistribution of phosphorylated ERK-1/2 and actin into membrane ruffles/lamellipodia or migration of MCF-7 HER2 cells. However, a migratory phenotype in these cells could be induced in response to S1P when SK1 expression had been knocked down with a specific siRNA or when recombinant PAK1 was ectopically overexpressed. Thus, the HER2-dependent increase in SK1 expression functions to desensitize the S1P-induced formation of a migratory phenotype. This is correlated with improved prognosis in patients who have a low HER1-3/SK1 expression ratio in their ER ؉ breast cancer tumors compared to patients that have a high HER1-3/SK1 expression ratio."Oncogene addiction" is a term that has been used to describe the reliance of cancer cells on the continued expression of oncogenes in order to maintain the diseased phenotype, progression, and metastasis of the cancer cell (39). Oncogene addiction is intrinsically susceptible to cross talk and feedback regulation that reflects abnormal signaling wiring in the cancer cell and which potentially makes these cells more susceptible to drug intervention at the level of the oncogene than normal cells. HER2 is a well-established oncogene that has an important role in enhancing breast cancer progression (2). The importance of its functional role as an addictive oncogene is exemplified by the fact that targeting HER2 with antibody mediated therapies, such as herceptin, demonstrates significant clinical efficacy (40). Indeed, this approach is in line with the concept that oncogene addiction is the "Achilles heel" of the cancer cell.There are four members of the human epidermal growth factor (EGF) receptor-related family, termed HER1 to HER4. The HER2/neu (c-erbB-2) gene encodes a 185-kDa transmembrane receptor tyrosine kinase, which is similar in amino acid sequence to other members of the EGF receptor family (30). Moreover, the overexpression of HER2/neu and gene amplification is found in up to 30% of primary breast cancers, and its expression is correlated with increased tumor invasion, poor prognosis, and therapeutic resistance (2). Overexpression of HER2 is also associated with downregulation of the estrogen receptor (ER) but not necessarily the complete elimination of...

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“…To this end, a long (2217 bp) and two shorter (1053 and 691 bp) fragments of the human SK-1 promoter were cloned according to Nakade et al (2003) and fused to a luciferase-containing vector. Transfection of MCF7 cells with these fragments followed by PRL or E 2 stimulation reveals that only the long 2217 bp promoter fragment is able to increase luciferase activity, whereas the two shorter fragments are ineffective (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…4). The human SK-1 promoter was first cloned by Nakade et al (2003) and it was shown to be highly stimulated by the direct PKC activator TPA. The involvement of PKC in PRL-induced SK-1 upregulation is confirmed by the blocking effect of the selective PKC inhibitor Ro 318220 (Fig.…”

Section: F Dö Ll Et Al: Prolactin Activates Sk-1 In Mcf7 Cellsmentioning

confidence: 99%

Prolactin upregulates sphingosine kinase-1 expression and activity in the human breast cancer cell line MCF7 and triggers enhanced proliferation and migration

Döll¹,

Pfeilschifter²,

Huwiler³

2007

Endocr Relat Cancer

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Sphingosine kinases (SK) catalyze the formation of sphingosine-1-phosphate (S1P) which plays a crucial role in cell growth and survival. Here, we show that prolactin (PRL) biphasically activates the SK-1, but not the SK-2 subtype, in the breast adenocarcinoma cell-line MCF7. A first peak occurs after minutes of stimulation and is followed by a second delayed activation after hours of stimulation. A similar biphasic effect on SK-1 activity is seen for 17b-estradiol (E 2 ). The delayed activation of SK-1 derives from an upregulated mRNA and protein expression and is due to increased SK-1 promoter activity and mechanistically involves STAT5 activation as well as protein kinase C and the classical mitogen-activated protein kinases. Furthermore, glucocorticoids also block both hormone-induced SK-1 expression and activity. Functionally, long-term stimulation of MCF7 cells with PRL or E 2 is well known to trigger increased cell proliferation and migration. Both hormone-induced cell responses critically involve SK-1 activation since the depletion of SK-1, but not SK-2, by siRNA transfection abolishes the hormone-induced cell proliferation and migration. In summary, our data show that PRL and E 2 cause a pronounced delayed SK-1 activation which is due to increased gene transcription, and critically determines the capability of cells to grow and move. Thus, the SK-1 may represent a novel attractive target for anti-tumor therapy.

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Regulation of sphingosine kinase 1 gene expression by protein kinase C in a human leukemia cell line, MEG-O1

Cited by 58 publications

References 48 publications

Role of sphingolipids in oestrogen signalling in breast cancer cells: an update

Role of sphingolipids in oestrogen signalling in breast cancer cells: an update

Sphingosine Kinase 1 Induces Tolerance to Human Epidermal Growth Factor Receptor 2 and Prevents Formation of a Migratory Phenotype in Response to Sphingosine 1-Phosphate in Estrogen Receptor-Positive Breast Cancer Cells

Prolactin upregulates sphingosine kinase-1 expression and activity in the human breast cancer cell line MCF7 and triggers enhanced proliferation and migration

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