Regulation of insulin‐like growth factor 1 binding protein 3 levels by epidermal growth factor and retinoic acid in cervical epithelial cells

Leyen, Sheila Andreatta‐Van; Hembree, Joan R.; Eckert, Richard L.

doi:10.1002/jcp.1041600208

Cited by 32 publications

(17 citation statements)

References 71 publications

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“…They may also affect cellular responses to EGFR ligands in modulating IGFBP-3 expression. For example, all-trans-retinoic acid induces IGFBP-3 in the presence of EGF at concentrations that suppress IGFBP-3 in cervical epithelial cell lines (32). Further complexity underlying EGFR-mediated regulation of IGFBP-3 was observed in that the effect of EGF stimulation on IGFBP-3 expression is different among the cell lines examined.…”

Section: Discussionmentioning

confidence: 99%

“…Another possibility is that IGFBP-3 inhibits tumor cell proliferation as a negative feedback mechanism. EGF treatment of human papilloma virus type 16-immortalized ectocervical epithelial cell lines results in decreased IGFBP-3 expression and concomitant enhancement of cell proliferation (32,59). Thus, it is possible that EGF-induced down-regulation of IGFBP-3 in TE2 and TE7 cells may facilitate the mitogenic effect of EGF in these cell lines.…”

Section: Discussionmentioning

confidence: 99%

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Epidermal Growth Factor Receptor Regulates Aberrant Expression of Insulin-Like Growth Factor-Binding Protein 3

et al. 2004

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Epidermal growth factor receptor (EGFR) is frequently overexpressed in esophageal carcinoma and its precursor lesions. To gain insights into how EGFR overexpression affects cellular functions in primary human esophageal cells, we performed gene expression profiling and identified insulin-like growth factor-binding protein (IGFBP)-3 as the most upregulated gene. IGFBP-3 regulates cell proliferation through both insulinlike growth factor-dependent and independent mechanisms. We found that IGFBP-3 mRNA and protein expression was increased in EGFRoverexpressing primary and immortalized human esophageal cells. IG-FBP-3 was also up-regulated in EGFR-overexpressing cells in organotypic culture and in EGFR transgenic mice. Furthermore, IGFBP-3 mRNA was overexpressed in 80% of primary esophageal squamous cell carcinomas and 60% of primary esophageal adenocarcinomas. Concomitant upregulation of EGFR and IGFBP-3 was observed in 60% of primary esophageal squamous cell carcinomas. Immunohistochemistry revealed cytoplasmic localization of IGFBP-3 in the preponderance of preneoplastic and neoplastic esophageal lesions. IGFBP-3 was also overexpressed in esophageal cancer cell lines at both mRNA (60%) and protein (40%) levels. IGFBP-3 secreted by cancer cells was capable of binding to insulinlike growth factor I. Functionally, epidermal growth factor appeared to regulate IGFBP-3 expression in esophageal cancer cell lines. Finally, suppression of IGFBP-3 by small interfering RNA augmented cell proliferation, suggesting that IGFBP-3 may inhibit tumor cell proliferation as a negative feedback mechanism. In aggregate, we have identified for the first time that IGFBP-3 is an aberrantly regulated gene through the EGFR signaling pathway and it may modulate EGFR effects during carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Regulates Aberrant Expression of Insulin-Like Growth Factor-Binding Protein 3

et al. 2004

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“…28,29 Even in a single cell line, there is not a strict correlation between IGFBP-3 levels and cell growth. In HPV-16-immortalized cervical epithelial cells, IGFBP-3 mRNA levels increase in response to retinoic acid, a growth suppressive factor 30 but decrease in response to transforming growth factor-␤, another growth suppressive factor. 31 It will be important now to determine directly the biological effect of IGFBP-3 on the growth and differentiation of normal and HPV-immortalized cervical epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Insulin-Like Growth Factor-Binding Protein 3 Expression Increases during Immortalization of Cervical Keratinocytes by Human Papillomavirus Type 16 E6 and E7 Proteins

Berger

Baege

Guillemette

et al. 2002

The American Journal of Pathology

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Human papillomaviruses (HPVs) are the major cause of cervical cancer and precancerous cervical lesions.1 Epidemiological and molecular studies have identified highrisk types of HPV, such as HPV-16 and HPV-18, which are present in Ͼ90% of high-grade cervical lesions and cervical cancers. In contrast, low-risk types of HPV such as HPV-6 and HPV-11 are found in genital warts and lowgrade cervical lesions but rarely in high-grade lesions or cancer. The difference between high-risk and low-risk HPV types is also apparent in cultured cells. The E6 and E7 oncogenes of high-risk HPV are sufficient to immortalize human foreskin keratinocytes and cervical epithelial cells in vitro. 2,3 In contrast, the E6 and E7 genes of low-risk HPV can prolong life span in culture but cannot immortalize cells. 4 This difference between viral types can be explained by the different interactions of high-risk and low-risk E6 and E7 with the key human cell-cycle regulatory proteins p53 and pRb. 5,6 Destabilization of p53 and pRb proteins by high-risk but not low-risk HPV oncogenes results in altered levels of other cell-cycle regulatory proteins. For example, levels of cyclin A, cyclin B, cyclin E, cdc2, cdk2, and cdk4 proteins are elevated in HPV-16 expressing keratinocytes 7,8 when compared to controls. Recent results from cDNA microarray experiments that surveyed several thousand genes indicate that mRNA levels of these cell cycle genes are also elevated in HPV-16 E6/E7 expressing keratinocytes. 9,10

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“…For instance, induction of cellular stress by ultraviolet irradiation inhibits ligand-induced transcription of RXR-RAR target genes (Wang et al, 1999). Peptide growth factors block the biological effects of retinoids by inhibiting the activity of the RAR and RXR receptors (Miller et al, 1993;Andreatta-Van Leyen et al, 1994). Interestingly, other studies involved insulin like growth factors (IGFs) and their interaction with retinoid signaling.…”

Section: Nuclear Receptor Rarb2 Activation and Beta Arrestin F Piu Et Almentioning

confidence: 99%

β-arrestin 2 modulates the activity of nuclear receptor RAR β2 through activation of ERK2 kinase

2005

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The activity of retinoid receptors activity can be regulated by various extracellular stimuli. In an effort to understand the molecular basis for this phenomenon, the role of b-arrestins was investigated. b-Arrestins constitute a class of proteins involved in the internalization of agonistactivated receptors. They have also been linked to MAPK activation suggesting a direct involvement in signaling cascades. Here, we report that b-arrestin 2 stimulates the transcriptional activation of the retinoid RAR and RXR receptors. Of all the retinoid receptors, the RAR b2 subtype showed the strongest sensitivity to b-arrestin 2 action. Interestingly, this event requires the presence of the MAP kinase ERK2, but not that of JNK or P38. Sitedirected mutagenesis showed that Ser 22 and Leu 217 are critical residues of the RAR b2 receptor through which b-arrestin 2 effects are mediated. More importantly, we demonstrate that the induction of PC12 growth inhibition by Nerve Growth Factor is indeed dependent upon RAR b2 transcriptional activation in a b-arrestin 2-and ERK2-dependent manner.

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Regulation of insulin‐like growth factor 1 binding protein 3 levels by epidermal growth factor and retinoic acid in cervical epithelial cells

Cited by 32 publications

References 71 publications

Epidermal Growth Factor Receptor Regulates Aberrant Expression of Insulin-Like Growth Factor-Binding Protein 3

Epidermal Growth Factor Receptor Regulates Aberrant Expression of Insulin-Like Growth Factor-Binding Protein 3

Insulin-Like Growth Factor-Binding Protein 3 Expression Increases during Immortalization of Cervical Keratinocytes by Human Papillomavirus Type 16 E6 and E7 Proteins

β-arrestin 2 modulates the activity of nuclear receptor RAR β2 through activation of ERK2 kinase

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