A c-mycAntisense Oligonucleotide Inhibits Human Retinal Pigment Epithelial Cell Proliferation

Capeáns, C.; Piñeiro, Antonio; Domı́nguez, Fernando; Loidi, Lourdes; Buceta, Montserrat; Carneiro, Carmen; García‐Caballero, Tomás; Sánchez-Salorio, Manuel

doi:10.1006/exer.1997.0452

Cited by 15 publications

(15 citation statements)

References 40 publications

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“…It has been also proposed that c-myc acts to sensitize cells to a variety of apoptotic triggers [Capeans et al, 1998]. Our studies of HL60 cancer cells demonstrate that the inhibition of AP-1 activity by NDGA or SP600125 induces apoptosis.…”

Section: Discussionmentioning

confidence: 68%

“…An oligomer, antisense, whose sequence was complementary to the first five codons (starting from the initiation codon) of human c-myc mRNA [Heikkila et al, 1987]: 5 0 aacgttgaggggcat 3 0 , and a second oligomer as a control, whose sequence is the same but in the opposite direction to the sequence of antisense oligomer [Capeans et al, 1998]: 5 0 tacggggagttgcaa 3 0 . To examine whether the treatment of antisense c-myc oligonucleotide blocks endogenous c-myc expression, we performed RT-PCR.…”

Section: Human C-myc Antisense Oligonucleotide and Rt-pcr Anaysismentioning

confidence: 99%

“…Previous studies have established that c-myc antisense oligonucleotide blocks the expression of myc [Capeans et al, 1998]. Experiments were performed to determine the effects of c-myc antisense oligonucleotide on the generation of apoptosis by AP-1 inhibitors.…”

Section: C-myc Antisense Treatment and Reversal Of Apoptosismentioning

confidence: 99%

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Inhibition of AP‐1 transcription activator induces myc‐dependent apoptosis in HL60 cells

Park

Hahm

Lee

et al. 2004

J of Cellular Biochemistry

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Transcriptional activation of AP-1 is intricately involved in cell proliferation and transformation. The natural product, nordihydroguaiaretic acid (NDGA) shows an inhibitory effect on the binding of jun/AP-1 protein to the AP-1 site in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated HL60 cells. The NDGA inhibits the auto-regulated de novo synthesis of c-jun mRNA in TPA-stimulated HL60 cells. Our data also determine that this compound induces proliferation inhibition and apoptosis in human leukemia HL60 cells. To obtain information on the functional role of the AP-1 inhibition by NDGA in apoptosis signaling, the effects of pharmacological inhibition of AP-1 binding on c-myc, p53, and bax protein level were determined. Our results indicate that treatment of cells with NDGA enhances c-myc, p53, and bax protein levels. To rule out the possibility that NDGA will induce apoptosis because of the effects on proteins other than AP-1, we investigated the effect of another AP-1 inhibitor, SP600125, which is specific to Jun-N-terminal kinase. SP600125 decreased not only the phosphorylation level of jun protein but also AP-1/DNA binding activity. Also, apoptosis was observed to be induced by SP600125, concomitant with the increase in c-myc, p53, and bax protein level. In addition, apoptosis induced by both AP-1 inhibitors was accompanied by the activation of a downstream apoptotic cascade such as caspase 9, caspase 3, and poly[ADP-ribose]polymerase (PARP). When the cells were treated with NDGA or SP600125 in the presence of antisense c-myc oligonucleotides, apoptosis was not observed and an increase of c-myc, p53, and bax proteins was not manifested. All these results show that the inhibition of the transcription factor AP-1 action is related with either the drug-induced apoptosis or the drug toxicity of the HL60 cells. The apoptosis induced by AP-1 inhibition may be dependent on c-myc protein levels suggesting that the c-myc protein induces apoptosis at a low level of AP-1 binding activity. Altogether, our findings suggest that the presence of the AP-1 signal acts as a survival factor that determines the outcome of myc-induced proliferation or apoptosis.

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Section: Discussionmentioning

confidence: 68%

Section: Human C-myc Antisense Oligonucleotide and Rt-pcr Anaysismentioning

confidence: 99%

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Inhibition of AP‐1 transcription activator induces myc‐dependent apoptosis in HL60 cells

Park

Hahm

Lee

et al. 2004

J of Cellular Biochemistry

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“…The human retinal pigment epithelial cell line (hRPE), previously established by our group [Capeans et al, 1998], was grown in DMEM media supplemented with antibiotics and 10% FBS.…”

Section: Cell Culturesmentioning

confidence: 99%

Abnormal cell cycle regulation in primary human uveal melanoma cultures

Pardo

Piñeiro

Fuente

et al. 2004

J of Cellular Biochemistry

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Uveal malignant melanoma is the most frequent primary intraocular tumor in adult humans. The cellular events leading to neoplasic transformation of normal uveal melanocytes are not well known when compared to other cancers. In this study, we investigated the role of G1 and G1/S regulatory proteins of the cell cycle in human uveal melanoma (UM) primary cell cultures, since these proteins are common targets in tumor development. Further, freshly established and characterized tumor cells are a better model for in vitro studies when compared to cell lines established long ago. Human primary cell cultures from eight different UM were established, as well as one primary culture from rhesus uveal normal melanocytes (UNM). Primary human UM cultures were characterized by a low establishment and growing rate. From four successful cultures, three showed a high expression of cyclin D1, cyclin E, p16NK4A, and p27KIP1 with no variations in cyclin A, cyclin-dependent kinase 2 (CDK2), and CDK4. Interestingly, in one of the cultured tumors, tumor suppressor protein retinoblastoma (Rb) did not bind E2F despite the fact that Rb was found in its hypophosphorylated form. No mutations in either RB1 or the Rb-binding pocket of E2F-1 were detected. Furthermore, we identified seven proteins co-immunoprecipitating with Rb in this tumor, including Lamin A/C and six proteins not previously reported to bind Rb: Hsc70, high mobility group protein 1 (HMG-1), hnRPN, glyceraldehyde 3 phosphate dehydrogenase (G3PDH), EF-1, and EF-2. Our results indicate that the overexpression of cyclins D1/E and CDKIs p16 and p27, together with a deregulation of the Rb/E2F pathway, may be implicated in the development of human UM.

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“…1 Oligonucleotides based on a nuclease resistant phosphorothioate backbone have proved to be very potent and selective inhibitors of protein expression in vitro as well as in vivo. 2,3 Despite this therapeutic potential, the detailed analysis of their whole chemical, biochemical and biophysical characteristics still indicates that this class of compounds may not represent the ®nal solution to the problem of designing functional antisense inhibitors. 4 2 0 -Modi®cations have also proved to have interesting hybridization properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and properties of (2′S)- and (2′R)-2′-deoxy-2′-C-methyl oligonucleotides

Cicero¹,

Gallo

Neuner³

et al. 2001

Tetrahedron

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A c-mycAntisense Oligonucleotide Inhibits Human Retinal Pigment Epithelial Cell Proliferation

Cited by 15 publications

References 40 publications

Inhibition of AP‐1 transcription activator induces myc‐dependent apoptosis in HL60 cells

Inhibition of AP‐1 transcription activator induces myc‐dependent apoptosis in HL60 cells

Abnormal cell cycle regulation in primary human uveal melanoma cultures

Synthesis and properties of (2′S)- and (2′R)-2′-deoxy-2′-C-methyl oligonucleotides

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