Human Chorionic Gonadotropin Suppresses Activation of Nuclear Transcription Factor-κB and Activator Protein-1 Induced by Tumor Necrosis Factor

Manna, Sunil K.; Mukhopadhyay, Asok; Aggarwal, Bharat B.

doi:10.1074/jbc.275.18.13307

Cited by 34 publications

(29 citation statements)

References 55 publications

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“…27,56 For example, the natural product Resveratrol inhibits AP-1 and NFκB activity and the subsequent activation of their target genes. [57][58][59][60] We have shown that the HIV-1 induced changes in DNMT1 expression 22,30 (Fig. 1) are most likely mediated through the transcription factor AP-1 (Fig.…”

Section: Discussionmentioning

confidence: 99%

The early expressed HIV-1 genes regulate DNMT1 expression

Youngblood¹,

Reich²

2008

Epigenetics

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Section: Discussionmentioning

confidence: 99%

The early expressed HIV-1 genes regulate DNMT1 expression

Youngblood¹,

Reich²

2008

Epigenetics

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“…NF-B and AP-1 are transcription factors, and hCG is known to inhibit their activation in a number of nongonadal cell types (42). This precedent, as well as the anti-breast cancer actions of hCG (10,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), led us to test whether hCG can inhibit their activation by TNF, which stimulates cell proliferation and invasion.…”

Section: Discussionmentioning

confidence: 99%

“…Various agents, such as TNF, that activate NF-B can also activate AP-1 (42,43). This led us to test whether hCG could block AP-1 activation induced by TNF.…”

Section: Effect Of Hcg On Phosphorylation and Degradation Of Ib␣-mentioning

confidence: 99%

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Human Chorionic Gonadotropin Decreases Proliferation and Invasion of Breast Cancer MCF-7 Cells by Inhibiting NF-κB and AP-1 Activation

Rao

Manna

et al. 2004

Journal of Biological Chemistry

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The epidemiological data suggest that breast cancer risk decreases in women who complete full-term pregnancy at a young age. Studies on a rat breast cancer model indicate that human chorionic gonadotropin (hCG), a hormone that is present in very high levels during pregnancy, could be responsible for this decrease. These findings, as well as those demonstrating the presence of functional luteinizing hormone (LH)/ hCG receptors in human breast cells, prompted us to investigate the anti-proliferative and anti-invasive effects of hCG in human breast cancer MCF-7 cells by down-regulating NF-B and AP-1 transcription factors. Treatment of MCF-7 cells with highly purified hCG resulted in a modest dose-dependent and hormone-specific decrease in cell proliferation. hCG treatment also decreased cell invasion, which was more dramatic than the decrease in cell proliferation. These hCG actions were abrogated when receptor synthesis was inhibited by treatment with antisense hCG/LH receptor phosphorothioate oligodeoxynucleotide. hCG treatment prevented the tumor necrosis factor-dependent NF-B and AP-1 activation, which paralleled a decrease in the phosphorylation and degradation of IB␣. The findings that hCG treatment increased cAMP synthesis and activated cAMP-dependent protein kinase, dibutyryl cAMP mimicked hCG in preventing NF-B activation, and dideoxyadenosine, an adenylate cyclase inhibitor, prevented the hCG effect on NF-B suggested that the hCG actions are mediated via the cAMP-dependent protein kinase A signaling pathway. In summary, our results demonstrate that hCG has anti-proliferative and antiinvasive effects in MCF-7 cells by down-regulating NF-B and AP-1. These findings support the premise that hCG could be responsible for the pregnancy-induced protection against breast cancer in women.

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“…Whereas both TNFα and p53 are known to stimulate the expression of JUN and AP1 activity 76, 87 , NKX3.1 expression did not significantly affect the mRNA level of cJUN (-1.21-fold change) or JUND (+1.25-fold change). However, the JUN interaction partner FOS was increased 3.9-fold by NKX3.1.…”

Section: Resultsmentioning

confidence: 83%

Systems analysis of the prostate tumor suppressor NKX3.1 supports roles in DNA repair and luminal cell differentiation

Yang

Chung²,

et al. 2014

F1000Res

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NKX3.1 is a homeobox transcription factor whose function as a prostate tumor suppressor remains insufficiently understood because neither the transcriptional program governed by NKX3.1, nor its interacting proteins have been fully revealed. Using affinity purification and mass spectrometry, we have established an extensive NKX3.1 interactome which contains the DNA repair proteins Ku70, Ku80, and PARP, thus providing a molecular underpinning to previous reports implicating NKX3.1 in DNA repair. Transcriptomic profiling of NKX3.1-negative prostate epithelial cells acutely expressing NKX3.1 revealed a rapid and complex response that is a near mirror image of the gene expression signature of human prostatic intraepithelial neoplasia (PIN). Pathway and network analyses suggested that NKX3.1 actuates a cellular reprogramming toward luminal cell differentiation characterized by suppression of pro-oncogenic c-MYC and interferon-STAT signaling and activation of tumor suppressor pathways. Consistently, ectopic expression of NKX3.1 conferred a growth arrest depending on TNFα and JNK signaling. We propose that the tumor suppressor function of NKX3.1 entails a transcriptional program that maintains the differentiation state of secretory luminal cells and that disruption of NKX3.1 contributes to prostate tumorigenesis by permitting luminal cell de-differentiation potentially augmented by defects in DNA repair.

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Human Chorionic Gonadotropin Suppresses Activation of Nuclear Transcription Factor-κB and Activator Protein-1 Induced by Tumor Necrosis Factor

Cited by 34 publications

References 55 publications

The early expressed HIV-1 genes regulate DNMT1 expression

The early expressed HIV-1 genes regulate DNMT1 expression

Human Chorionic Gonadotropin Decreases Proliferation and Invasion of Breast Cancer MCF-7 Cells by Inhibiting NF-κB and AP-1 Activation

Systems analysis of the prostate tumor suppressor NKX3.1 supports roles in DNA repair and luminal cell differentiation

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