CREB and Its Associated Proteins Act as Survival Factors for Human Melanoma Cells

Jean, Didier; Harbison, Matthew T.; McConkey, David J.; Ronai, Ze’ev A.; Bar‐Eli, Menashe

doi:10.1074/jbc.273.38.24884

Cited by 151 publications

(123 citation statements)

References 38 publications

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“…Many oncogenes have been shown to encode proteins that trasmit mitogenic signals upstream of the MAPK pathway (Seger and Krebs, 1995;Sebolt-Leopold, 2000). Phosphorylation of CREB generates signals that inhibit apotosis (Jean et al, 1998;Jean and Bar-Eli, 2000). Control of phosphorylation in gastrointestinal malignancies has recently been reported as an important mechanism for some neoplasia (Saha et al, 2001;Higashi et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

DARPP-32 expression arises after a phase of dysplasia in oesophageal squamous cell carcinoma

et al. 2004

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This is the first report to correlate DARPP-32 immunoreactivity (dopamine and cAMP-regulated phosphoprotein, M r 32 000) to clinicopathological status in human cancer. DARPP-32 is recognised as a neuronal protein. A recent study demonstrated that DARPP-32, and a truncated isoform t-DARPP, are overexpressed in gastric carcinoma during the process of carcinogenesis. The biological function of DARPP-32, however, is still unclear. The purpose of this study was to clarify the roles of DARPP-32 and t-DARPP in oesophageal squamous cell carcinoma (OSCC). Initially, we investigated DARPP-32 and t-DARPP expression in OSCC cell lines by Reverse transcription -polymerase chain reaction and Western blot. DARPP-32 expression was observed in four out of seven (57.1%) cell lines, but t-DARPP expression was not observed in any cell lines. In oesophageal tissue sample, DARPP-32 expression was observed in four out of seven (57.1%) tumour tissues, while t-DARPP was not observed in any tissues. Subsequently, DARPP expression was assessed by immunohistochemistry, using a polyclonal antibody, in tissue sections from 122 patients with primary OSCC. DARPP immunoreactivity was not observed in any normal oesophageal mucous membranes. On the other hand, positive DARPP immunostaining was detected in 37 patients (30.3%) and correlated inversely with pathologic stage (P ¼ 0.0284), pT (P ¼ 0.0438), pN (P ¼ 0.0303) and tumour size (P ¼ 0.012). The overall survival rate was worse in patients with DARPP-negative tumours than in patients with DARPP-positive tumours (P ¼ 0.0453). Interestingly, DARPP expression was observed in only one out of 45 cases of dysplasia. These observations suggest that DARPP-32 (rather than t-DARPP) expression arises after a phase of dysplasia in OSCC, and that tumours expressing DARPP-32 progress less rapidly than DARPP-32-negative tumours.

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Section: Discussionmentioning

confidence: 99%

DARPP-32 expression arises after a phase of dysplasia in oesophageal squamous cell carcinoma

et al. 2004

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“…Recent evidence supports the belief that a variety of transcription factors are important in the pathogenesis of melanoma, including activating transcription factor-1 (ATF-1) (Bohm et al, 1995;, cAMP response elementbinding protein (CREB) Jean et al, 1998b;Rutberg et al, 1994;Xie et al, 1997b), transcription factor AP-2 (Huang et al, 1998;Jean et al, 1998a), micropthalmia transcription factor (Mitf) (Goding, 2000;King et al, 1999;Fang and Setaluri, 1999), and nuclear factor-kappa B (NF-kB) . In particular, we have previously demonstrated that the transition of melanoma to the metastatic phenotype is associated with a loss of expression of the transcription factor AP-2 (Bar- Eli, 1997Eli, , 1999).…”

Section: Introductionmentioning

confidence: 99%

Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growth in vivo

et al. 2001

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We have previously demonstrated that the transition of melanoma to the metastatic phenotype is associated with a loss of expression of the transcription factor AP-2. To further investigate the role of AP-2 in the progression of human melanoma, we attempted to inactivate AP-2 in primary cutaneous SB-2 melanoma cells by using a dominant-negative AP-2, or AP-2B, gene. AP-2B is an alternatively spliced AP-2 variant capable of inhibiting AP-2 trans-activator function. Stable transfection of primary cutaneous melanoma SB-2 cells with the dominant-negative AP-2B gene was con®rmed by RT ± PCR and Northern blot analyses. Electromobility shift assay using nuclear extracts from these cell lines demonstrated decreased functional binding of AP-2B-transfected cells to the AP-2 consensus binding sequence compared with neo-transfected controls. In addition, CAT activity driven by a construct containing the AP-2 consensus binding sequence was downregulated in the AP-2B transfected cells, indicating AP-2 activity was quenched in the transfected cells. Orthotopic (subcutaneous) injection of the dominant-negative (AP-2B)-transfected cell lines into nude mice increased their tumorigenicity compared to control neo-transfected cells. The AP-2B-transfected cells displayed an increase in MMP-2 expression (by Northern blot) and MMP-2 activity (by zymography), which resulted in an increase in invasiveness through Matrigel-coated ®lters. The AP-2B-transfected tumors also displayed an increase in MMP-2 expression, microvessel density, and angiogenesis in vivo. These results demonstrate that inactivation of AP-2 contributes to the progression of melanoma, at least partially via deregulation of the MMP-2 gene.

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“…CREB is also associated with the prevention of apoptosis in melanoma cells, however, the authors of that study were unable to correlate the inhibition of apoptosis with changes in the level of Bcl-2, Bcl-X L , Bad or Bax expression. 105 In addition, p90 Rsk may have anti-apoptotic effects independent of the transcription of anti-apoptotic genes. p90 Rsk has been shown to phosphorylate BAD on serine residue 112.…”

Section: The Ras/raf/mek/erk Signaling Kinase Cascadementioning

confidence: 99%

Kinases: positive and negative regulators of apoptosis

2000

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Cells sense and respond to extracellular factors via receptors on the cell surface that trigger intracellular signaling pathways. The signals received by the receptors on hematopoietic cells often determine if the cell proliferates, survives or undergoes apoptosis. Apoptosis can be induced by almost any cytotoxic stimuli. These stimuli may be an absence of signals arising from cellular receptors, stimulation of specific ligand receptors on the cell surface, chemotherapeutic agents, and ionizing radiation or oxygen radicals, as well as a number of other factors. Cellular kinases and phosphatases participate in signaling cascades that influence this process. We review the ability of the calmodulin-dependent-kinases, I-B kinases, PI3-kinases, Jakkinases, PKC, PKA, and MAP kinase signaling pathways (Erk, Jnk, and p38), to influence the apoptotic process. In addition, we discuss the cross-talk that exists between signaling cascades that are pro-apoptotic and anti-apoptotic.

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CREB and Its Associated Proteins Act as Survival Factors for Human Melanoma Cells

Cited by 151 publications

References 38 publications

DARPP-32 expression arises after a phase of dysplasia in oesophageal squamous cell carcinoma

DARPP-32 expression arises after a phase of dysplasia in oesophageal squamous cell carcinoma

Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growth in vivo

Kinases: positive and negative regulators of apoptosis

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