Attenuation of matrix protein secretion by antisense oligodeoxynucleotides to the cyclin kinase inhibitor p21Waf1/Cip1

Weiss, Robert H.; Randour, Collette J

doi:10.1016/s0021-9150(01)00628-1

Cited by 15 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Utilization of antisense ODN to p21 in vivo and in vitro has been shown to be a sensitive way to examine its role in inhibition of cell proliferation, angiogenesis, matrix protein production, and induction of apoptosis (35,44,54). Our results in p21 antisense experiments showed that this ODN antagonized PPAR␥ ligand induction of p21 protein and suppression of lung carcinoma cell growth.…”

Section: Discussionmentioning

confidence: 67%

“…Phosphorothioate p21 antisense and random sequence control oligodeoxynucleotides (ODN) designed around the translation start site were synthesized by Sigma Genoys according to published data (35). The p21 antisense sequence was 5Ј-GAC ATCACCAGGATC-GGACAT-3Ј.…”

Section: Methodsmentioning

confidence: 99%

“…An earlier study showed that p21 antisense ODN can reduce p21 protein levels in both animal and human cells (35,44). To determine whether similar effects are observed in lung carcinoma cells, H1838 cells were transfected with p21 phosphorothioate ODN or control random ODN.…”

Section: Induction Of P21 Gene Expression By Ppar␥ Ligandsmentioning

confidence: 99%

See 2 more Smart Citations

Up-regulation of p21 Gene Expression by Peroxisome Proliferator-Activated Receptor γ in Human Lung Carcinoma Cells

Han

Sidell

Fisher

et al. 2004

Clinical Cancer Research

127

103

View full text Add to dashboard Cite

Purpose: The peroxisome proliferator-activated receptor ␥ (PPAR␥), a ligand-dependent transcription factor belonging to the family of nuclear receptors, has been implicated in the regulation of cell growth and differentiation although the exact mechanism(s) of this activity has not been elucidated. In this study, we explored the role of PPAR␥ signaling on the control of gene expression of the cycledependent kinase inhibitor p21 in human lung carcinoma cells.Experimental Design: Using several human lung carcinoma cell lines (small and non-small carcinoma cells), we assayed for cell growth inhibition and apoptosis induction. We also assayed for p21 mRNA and protein expression by reverse transcription-PCR, real-time reverse transcription-PCR, and Western blot analysis. Nuclear protein binding activities to three response elements located in the p21 promoter [nuclear factor (NF)-B, Sp1, and NF-interleukin 6 (IL6) CAAT/enhancer binding protein (C/EBP)] were measured by gel mobility shift assays. We used transient transfection assays with p21 promoter reporter gene constructs to determine the transcriptional regulation by PPAR␥ ligands. Finally, by using p21 antisense oligonucleotides, we tested the link between PPAR␥ activation and p21 signaling in cell growth inhibition assays and by Western blot analysis.Results: We showed that the PPAR␥ ligands PGJ2 and ciglitazone inhibit the growth and induce the apoptosis of several human lung carcinoma cell lines, whereas the PPAR␣ agonist WY14643 has little effect. Treatment of lung carcinoma cells with the PPAR␥ ligands PGJ2, ciglitazone, troglizaone, and GW1929 elevated p21 mRNA and protein levels and reduced cyclin D1 mRNA levels. These results were supported by transient transfection assays, which indicated that PPAR␥ ligands increased p21 gene promoter activity in human lung carcinoma cells. In addition, p21 antisense oligonucleotides inhibited PPAR␥ ligand-induced p21 protein expression and significantly blocked lung carcinoma cell growth inhibition induced by PPAR␥ ligands. Finally, electrophoresis mobility shift experiments demonstrated that PPAR␥ ligands increased the nuclear binding activities of Sp1 and NF-IL6 (C/EBP), two transcription factors with regulatory elements in the promoter region of the p21 gene.Conclusion: PPAR␥ ligands inhibit human lung carcinoma cell growth and induce apoptosis by stimulating the cyclin-dependent kinase inhibitor p21 and by reducing cyclin D1 gene expression. The induction of p21 gene expression by PPAR␥ ligands may be mediated through increased Sp1-and NF-IL6 (C/EBP)-dependent transcriptional activation. These observations unveil a mechanism for p21 gene regulation in lung carcinoma that represents a potential target for therapy.

show abstract

Section: Discussionmentioning

confidence: 67%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Up-regulation of p21 Gene Expression by Peroxisome Proliferator-Activated Receptor γ in Human Lung Carcinoma Cells

Han

Sidell

Fisher

et al. 2004

Clinical Cancer Research

127

103

View full text Add to dashboard Cite

show abstract

“…It is also noteworthy that specific inhibition of p21 by transfer of antisense oligonucleotides does not abolish the growth-inhibitory effect of transforming growth factor-␤ in cultured SMCs, yet it markedly reduces both the synthesis and secretion of laminin and fibronectin. 15 Thus, diminished matrix protein deposition may attenuate atherosclerosis in p21 Ϫ/Ϫ apoE Ϫ/Ϫ mice. Because excessive cell growth is thought to contribute to atheroma development 5,6 and p21 is generally considered a growth suppressor, 4 one must also reflect on cellular proliferation when considering the provocative study by Merched and Chan.…”

Section: Why P21 Disruption Protects Apoe-null Mice From Atherosclerosismentioning

confidence: 99%

Unexpected Proatherogenic Properties of p21

Andrés

2004

Circulation

View full text Add to dashboard Cite

“…This result could be related to the observations that chlorate-induced reduction of sulfation of HS chains of the perlecan proteoglycan in C2C12 myoblasts diminished their differentiation capacity (Villar et al, 1999). Stimulation of proliferation has been shown to correlate with an increase in matrix protein (Porcionatto et al, 1998) and HSPG secretions in endothelial cells (Weiss and Randour, 2002). Conversely, changes in HS sulfation might alter HBGF synthesis and intracellular processing.…”

Section: Discussionmentioning

confidence: 74%

A synthetic glycosaminoglycan mimetic (RGTA) modifies natural glycosaminoglycan species during myogenesis

Barbosa

Morin

Garcia

et al. 2005

Journal of Cell Science

View full text Add to dashboard Cite

Crucial events in myogenesis rely on the highly regulated spatiotemporal distribution of cell surface heparan sulfate proteoglycans to which are associated growth factors, thus creating a specific microenvironment around muscle cells. Most growth factors involved in control of myoblast growth and differentiation are stored in the extracellular matrix through interaction with specific sequences of glycosaminoglycan oligosaccharides, mainly heparan sulfate (HS). Different HS subspecies revealed by specific antibodies, have been shown to provide spatiotemporal regulation during muscle development. We have previously shown that glycosaminoglycan (GAG) mimetics called RGTA (ReGeneraTing Agent), stimulate muscle precursor cell growth and differentiation. These data suggest an important role of GAGs during myogenesis; however, little is yet known about the different species of GAGs synthesized during myogenesis and their metabolic regulation. We therefore quantified GAGs during myogenesis of C2.7 cells and show that the composition of GAG species was modified during myogenic differentiation. In particular, HS levels were increased during this process. In addition, the GAG mimetic RGTA, which stimulated both growth and differentiation of C2.7 cells, increased the total amount of GAG produced by these cells without significantly altering their rate of sulfation. RGTA treatment further enhanced HS levels and changed its sub-species composition. Although mRNA levels of the enzymes involved in HS biosynthesis were almost unchanged during myogenic differentiation, heparanase mRNA levels decreased. RGTA did not markedly alter these levels. Here we show that the effects of RGTA on myoblast growth and differentiation are in part mediated through an alteration of GAG species and provide an important insight into the role of these molecules in normal or pathologic myogenic processes.

show abstract

Attenuation of matrix protein secretion by antisense oligodeoxynucleotides to the cyclin kinase inhibitor p21Waf1/Cip1

Cited by 15 publications

References 35 publications

Up-regulation of p21 Gene Expression by Peroxisome Proliferator-Activated Receptor γ in Human Lung Carcinoma Cells

Up-regulation of p21 Gene Expression by Peroxisome Proliferator-Activated Receptor γ in Human Lung Carcinoma Cells

Unexpected Proatherogenic Properties of p21

A synthetic glycosaminoglycan mimetic (RGTA) modifies natural glycosaminoglycan species during myogenesis

Contact Info

Product

Resources

About