Bryostatin 1 antagonizes the terminal differentiating action of 12-<i>O</i>-tetradecanoylphorbol-13-acetate in a human colon cancer cell

McBain, John A.; Pettit, George R.; Mueller, Gerald C.

doi:10.1093/carcin/9.1.123

Cited by 28 publications

(29 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These potential binding sites for the AP-2 transcription factor possess the following two important features: (a) their binding and transcriptional activity are inhibited by SV40 T antigen, and (b) they confer phorbol ester 12-O-tetradecanoylphorbol-13-acetate and cAMP inducibility (39). Of note, SV40 large T antigen inhibits transcription of perlecan in renal tubular epithelial cells (40), and perlecan expression is markedly up-regulated by 12-O-tetradecanoylphorbol-13-acetate in colon cancer (41) or K562 leukemia (6) cells. The proximal promoter region also contained three palindromic inverted repeats in close proximity of each other (between Ϫ438 and Ϫ204) that, by forming secondary structure, could influence the regulation of perlecan gene expression.…”

Section: Resultsmentioning

confidence: 99%

Structural and Functional Characterization of the Human Perlecan Gene Promoter

Iozzo

Pillarisetti²,

Sharma³

et al. 1997

Journal of Biological Chemistry

100

View full text Add to dashboard Cite

Perlecan, a modular heparan sulfate proteoglycan of basement membranes and cell surfaces, plays a crucial role in regulating the assembly of extracellular matrices and the binding of nutrients and growth factors to target cells. To achieve a molecular understanding of perlecan gene regulation, we isolated the 5-flanking region and investigated its functional promoter activity and its response to cytokines. Transient cell transfection assays, using plasmid constructs harboring the perlecan promoter linked to the chloramphenicol acetyltransferase reporter gene, demonstrated that the largest ϳ2.5-kilobase construct contained maximal promoter activity. This promoter region was functionally active in a variety of cells of diverse histogenetic origin, thus corroborating the widespread expression of this gene product. Stepwise 5 deletion analyses demonstrated that the ؊461-base pair (bp) proximal promoter retained ϳ90% of the total activity, and internal deletions confirmed that the most proximal sequence was essential for proper promoter activity. Nanomolar amounts of transforming growth factor-␤ induced 2-3-fold perlecan mRNA and protein core levels in normal human skin fibroblasts, and this induction was transcriptionally regulated; in contrast, tumor necrosis factor-␣ had no effect and was incapable of counteracting the effects of TGF-␤. Using additional 5 deletions and DNase footprinting analyses, we mapped the TGF-␤ responsive region to a sequence of 177 bp contained between ؊461 and ؊285. This region harbored a 14-bp element similar to a TGF-␤-responsive element present in the promoters of collagen ␣1(I), ␣2(I), elastin, and growth hormone. Electrophoretic mobility shift assays and mutational analyses demonstrated that the perlecan TGF-␤-responsive element bound specifically to TGF-␤-inducible nuclear proteins with high affinity for NF-1 member(s) of transcription factors.

show abstract

Section: Resultsmentioning

confidence: 99%

Structural and Functional Characterization of the Human Perlecan Gene Promoter

Iozzo

Pillarisetti²,

Sharma³

et al. 1997

Journal of Biological Chemistry

100

View full text Add to dashboard Cite

show abstract

“…Notably, the AP2 transcription factors can be suppressed by SV40 T antigen and can confer phorbol ester and cAMP induction (55). These cognate cis-acting elements are very likely to be operational in vivo since SV40 T antigen inhibits transcription of perlecan in renal tubular epithelial cells (56), whereas perlecan expression is markedly upregulated by phorbol ester in colon cancer (57) and in erythroleukemia K562 (58) cells, respectively. The perlecan promoter also contains several motifs that bind transcription factors involved in hematopoiesis, including two PEA3 motifs and nine GATA-1 motifs that are involved in erythrocyte differentiation (59).…”

Section: Genomic Organization and Transcriptional Controlmentioning

confidence: 99%

MATRIX PROTEOGLYCANS: From Molecular Design to Cellular Function

Iozzo

1998

Annu. Rev. Biochem.

1,483

1,111

View full text Add to dashboard Cite

The proteoglycan superfamily now contains more than 30 full-time molecules that fulfill a variety of biological functions. Proteoglycans act as tissue organizers, influence cell growth and the maturation of specialized tissues, play a role as biological filters and modulate growth-factor activities, regulate collagen fibrillogenesis and skin tensile strength, affect tumor cell growth and invasion, and influence corneal transparency and neurite outgrowth. Additional roles, derived from studies of mutant animals, indicate that certain proteoglycans are essential to life whereas others might be redundant.The review focuses on the most recent genetic and molecular biological studies of the matrix proteoglycans, broadly defined as proteoglycans secreted into the pericellular matrix. Special emphasis is placed on the molecular organization of the protein core, the utilization of protein modules, the gene structure and transcriptional control, and the functional roles of the various proteoglycans. When possible, proteoglycans have been grouped into distinct gene families and subfamilies offering a simplified nomenclature based on their protein core design. The structure-function relationship of some paradigmatic proteoglycans is discussed in depth and novel aspects of their biology are examined. CONTENTS

show abstract

“…PKC ~5 was shown to exert antiproliferative actions upon overexpression in CHO [7] or NIH 3T3 cells [8,9] and to cause differentiation in myeloid 32D cells [10]. PKC 8 is also a candidate for mediating the antiproliferative effects of phorbol esters observed in some pituitary and colon carcinoma cell lines [11,12]. Its mode of regulation may determine long-term responses of cells to prolonged activation of PKC in vivo, in particular with regard to the regulation of proliferation [13].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of PKC δ‐ and downregulation of PKC α‐mRNA and protein by a phorbol ester in human T84 cells

1996

View full text Add to dashboard Cite

Protein kinase C (PKC) family members are downregulated by chronic activation at the protein level in most cell types. In T84 human epithelial cells 12-O-tetradecanoyl phorbol 13-acetate (TPA) caused persistent translocation of PKC 8 to the membrane compartment and a 400% increase of PKC 5-mRNA after 24 h. In contrast, PKC a protein was completely downregulated and its mRNA was decreased to 60% of control levels after 24 h. This is the first report of PKC 5-mRNA upregulation by TPA which was previously only shown for PKC[~. In view of the antimitogenic actions of PKC 5 this pattern of regulation may serve to preserve growth control even in the presence of chronic cell activation.

show abstract

Bryostatin 1 antagonizes the terminal differentiating action of 12-O-tetradecanoylphorbol-13-acetate in a human colon cancer cell

Cited by 28 publications

References 0 publications

Structural and Functional Characterization of the Human Perlecan Gene Promoter

Structural and Functional Characterization of the Human Perlecan Gene Promoter

MATRIX PROTEOGLYCANS: From Molecular Design to Cellular Function

Upregulation of PKC δ‐ and downregulation of PKC α‐mRNA and protein by a phorbol ester in human T84 cells

Contact Info

Product

Resources

About