The Biphasic Induction of p21 and p27 in Breast Cancer Cells by Modulators of cAMP Is Posttranscriptionally Regulated and Independent of the PKA Pathway

Rao, Sharmila; Gray-Bablin, Julie; Herliczek, Thaddeus W; Keyomarsi, Khandan

doi:10.1006/excr.1999.4620

Cited by 19 publications

(18 citation statements)

References 65 publications

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“…This is also the reason why the time of stimulation for forskolin and dibutyryl-cAMP was chosen to be 4 h rather than 24 h in our study. Interestingly, a similar T-H Lee et al observation has also been reported in human breast cancer cells (Rao et al, 1999). The authors found that p21 WAF1 mRNA in human breast cancer cells peaked at 4 to 6 h after addition of cAMP modulators and gradually diminished, returning to basal level by 12 h. These results suggest that action of Tam in the induction of p21 WAF1 is dierent from that of PKA activators.…”

Section: Waf1supporting

confidence: 75%

“…Second, as described in Introduction, Tam may raise intracellular cAMP level by inhibiting cAMP-dependent phosphodiesterase and increased cAMP may subsequently activate PKA in cells. However, recent studies showed that cAMP may aect cellular functions via PKA-dependent and -independent signaling pathways (Cass et al, 1999;Rao et al, 1999). Although our results showed that H89 suppressed Tam-induced p21 WAF1 , the possibility that this drug may also inhibit other signaling pathways in cells could not be ruled out.…”

Section: Waf1contrasting

confidence: 71%

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Induction of p21WAF1 expression via Sp1-binding sites by tamoxifen in estrogen receptor-negative lung cancer cells

2000

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Section: Waf1supporting

confidence: 75%

Section: Waf1contrasting

confidence: 71%

Induction of p21WAF1 expression via Sp1-binding sites by tamoxifen in estrogen receptor-negative lung cancer cells

2000

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“…Together, the increased levels of cyclins and the decreased association of CdkIs lead to Cdk2 activation and progression to S phase (8). Although this model is widely accepted, mitogens and anti-mitogens can also affect progression through G 1 in other ways, for example by regulating the levels of CdkIs (32,33), the assembly and nuclear import of cyclinCdk complexes (34), or the levels and activity of Cdk-activating kinases or phosphatases (13)(14)(15).…”

Section: Many Estrogen Receptor (Er)mentioning

confidence: 99%

The Cyclin-dependent Kinase Inhibitor p21WAF1/Cip1 Is an Antiestrogen-regulated Inhibitor of Cdk4 in Human Breast Cancer Cells

Skildum

Mukherjee

Conrad

2002

Journal of Biological Chemistry

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The MCF-7 cell line is a model of estrogen-dependent, antiestrogen-sensitive human breast cancer. Antiestrogen treatment of MCF-7 cells causes dramatic decreases in both Cdk4 and Cdk2 activities, which leads to a G 1 phase cell cycle arrest. In this report, we investigate the mechanism(s) by which Cdk4 activity is regulated in MCF-7 cells. Through time course analysis, we demonstrate that changes in Cdk4 activity in response to estrogen or antiestrogen treatment do not correlate directly with cyclin D1 protein levels or association. In contrast, Cdk4 activity does correlate with changes in the level of the Cdk inhibitor p21 WAF1/Cip1 . Furthermore, we show that extracts of antiestrogen-treated cells contain a factor capable of inhibiting the Cdk4 activity present in extracts of estrogen-treated cells, and immunodepletion experiments identify this factor as p21 WAF1/Cip1 . These results identify p21 WAF1/Cip1 as an important physiological regulator of Cdk4 complexes in human breast cancer cells.

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“…Kip1 has been also implicated as a mediator of the growth arrest due to its regulation by protein kinase A activating agents (26). IH-901 stimulated p27…”

Section: Introductionmentioning

confidence: 99%

Cyclooxygenase-2 Inhibits Novel Ginseng Metabolite-Mediated Apoptosis

Yim¹,

Jong²,

Kim³

et al. 2005

Cancer Research

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Recently, a novel intestinal bacterial metabolite of ginseng protopanaxadiol saponins, i.e., 20-O-(B-D-glucopyranosyl)-20(S)-protopanaxadiol (IH-901), has been reported to induce apoptosis in a variety of cancer cells. Here we show a differential effect of IH-901 on several cell types. Exposure to IH-901 for 48 hours at a supposedly subapoptotic concentration of 40 A Amol/L led to both apoptotic cell death and G 1 arrest in Hep3B cells, but only resulted in G 1 arrest in MDA-MB-231, Hs578T, and MKN28 cells. Additionally, the treatment of MDA-MB-231, but not of Hep3B, with IH-901 up-regulated cyclooxygenase-2 (COX-2) mRNA (2 hours) and protein (6 hours), and enhanced the production of prostaglandin E 2 . In MDA-MB-231 cells, IH-901 induced the sustained activation of extracellular signal-regulated kinase (ERK), whereas inhibition of mitogen-activated protein/ERK kinase blocked IH-901-mediated COX-2 induction and resulted in apoptosis, suggesting the involvement of an ERK-COX-2 pathway. Combined treatment with IH-901 and nonsteroidal anti-inflammatory drugs inhibited COX-2 enzyme and induced apoptosis in MDA-MB-231 and Hs578T cells. Adenovirus-mediated COX-2 small interfering RNAs also effectively inhibited COX-2 protein expression and enhanced IH-901-mediated apoptosis without inhibiting ERK 1/2 phosphorylation, thus providing direct evidence that COX-2 is an antiapoptotic molecule. Moreover, IH-901-mediated G 1 arrest resulted from an increase in p27Kip1 mRNA and protein expression followed by a decrease in CDK2 kinase activity that was concurrent with the hypophosphorylation of Rb and p130. In conclusion, IH-901 induced both G 1 arrest and apoptosis, and this apoptosis could be inhibited by COX-2 induction. (Cancer Res 2005; 65(5): 1952-60)

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The Biphasic Induction of p21 and p27 in Breast Cancer Cells by Modulators of cAMP Is Posttranscriptionally Regulated and Independent of the PKA Pathway

Cited by 19 publications

References 65 publications

Induction of p21WAF1 expression via Sp1-binding sites by tamoxifen in estrogen receptor-negative lung cancer cells

Induction of p21WAF1 expression via Sp1-binding sites by tamoxifen in estrogen receptor-negative lung cancer cells

The Cyclin-dependent Kinase Inhibitor p21WAF1/Cip1 Is an Antiestrogen-regulated Inhibitor of Cdk4 in Human Breast Cancer Cells

Cyclooxygenase-2 Inhibits Novel Ginseng Metabolite-Mediated Apoptosis

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