AP-1 (Fos/Jun) transcription factors in hematopoietic differentiation and apoptosis.

Liebermann, Dan A.; Gregory, Bernard; Hoffman, Barbara

doi:10.3892/ijo.12.3.685

Cited by 93 publications

(102 citation statements)

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“…These studies have shown that in fibroblasts, AP-1 is an important regulator of proliferation and transformation (Brown et al, 1993;Rapp et al, 1994). Other studies, done in neuronal cells and in hematopoeitic cells, show that AP-1 regulates apoptosis (Ham et al, 1995;Liebermann et al, 1998). The current study demonstrates that in breast cancer cells, AP-1 is a critical regulator of proliferation.…”

Section: Discussionmentioning

confidence: 59%

Inhibition of AP-1 transcription factor causes blockade of multiple signal transduction pathways and inhibits breast cancer growth

et al. 2002

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AP-1 transcription factors play a critical role in signal transduction pathways in many cells. We have investigated the role of AP-1 in controlling proliferative signals in breast cells, and have previously shown that AP-1 complexes are activated by peptide and steroid growth factors in both normal and malignant breast cells. In this study, we investigated the role of AP-1 in transducing proliferative signals induced by peptide and steroid growth factors. We used MCF-7 clones that express a specific inhibitor of AP-1, a dominantnegative cJun mutant (TAM67), under the control of an inducible promoter to investigate the role of AP-1 in regulating breast cancer growth. In the presence of doxycycline (Dox), the AP-1 inhibitor was not expressed, and the MCF-7 clones proliferated normally in response to serum stimulation. However, when Dox was withdrawn, TAM67 was expressed, AP-1 activity was inhibited, and serum-induced proliferation was blocked. We next investigated whether the mitogenic response to specific growth factors also requires AP-1. MCF-7 Tet-Off-TAM67 cells were grown in the presence of increasing concentrations of IGF-1, EGF, heregulin-b, bFGF, or estrogen under un-induced and induced conditions. These studies showed that the AP-1 inhibitor completely blocked proliferation in response to the peptide growth factors (IGF-1, EGF, heregulin-b, and bFGF), and partially blocked the response to estrogen. To investigate the effect of AP-1 blockade on in vivo tumor growth, we injected the MCF-7 TetOff TAM67 cells into nude mice receiving doxycycline to suppress the expression of the AP-1 inhibitor. After the mice developed tumors, they were randomized to either continue to receive Dox or not. In mice not receiving Dox, the expression of TAM67 was induced, and tumor growth was inhibited, while the tumors in mice receiving Dox continued to grow. Analysis of the tumors from these mice showed that the expression of TAM67 caused reduced proliferation of the breast cancer cells without inducing apoptosis. These results demonstrate that AP-1 blockade supresses mitogenic signals from multiple different peptide growth factors as well as estrogen, and inhibits the growth of MCF-7 breast cancer cells both in vitro and in vivo. These results suggest that novel agents specifically targeting AP-1 or its activating kinases could be promising agents for the treatment of breast cancer.

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Section: Discussionmentioning

confidence: 59%

Inhibition of AP-1 transcription factor causes blockade of multiple signal transduction pathways and inhibits breast cancer growth

et al. 2002

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“…41) Previous studies have demonstrated that AP-1 is an important regulator of proliferation, transformation, and apoptosis, depending on the cell type. 42,43) An electrophoretic mobility shift analysis revealed that an increase in the DNA binding activity of AP-1 induced by STZ was inhibited by KIOM-79, and suggesting that the AP-1 pathway may be involved in the protective effect of KIOM-79 on cell apoptosis. Our results, threrfore, indicate that inhibition of ERK by KIOM-79 down-regulates the activation of the AP-1 transcription factor.…”

Section: Discussionmentioning

confidence: 99%

Cytoprotective Effects of KIOM-79 on Streptozotocin Induced Cell Damage by Inhibiting ERK and AP-1

Kang

Lee

Kim

et al. 2007

Biological & Pharmaceutical Bulletin

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“…In addition, CHOP interacts with members of the AP-1 transcription factor family to activate the transcription of specific genes. 33 AP-1 transcription factors play multiple roles in granulocytic differentiation, 34 and CHOP may modify their activities. CHOP also exerts antiproliferative and proapoptotic effects on cells.…”

Section: Discussionmentioning

confidence: 99%

Retinoic acid regulates C/EBP homologous protein expression (CHOP), which negatively regulates myeloid target genes

Gery

Park

Vuong

et al. 2004

Blood

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AP-1 (Fos/Jun) transcription factors in hematopoietic differentiation and apoptosis.

Cited by 93 publications

References 0 publications

Inhibition of AP-1 transcription factor causes blockade of multiple signal transduction pathways and inhibits breast cancer growth

Inhibition of AP-1 transcription factor causes blockade of multiple signal transduction pathways and inhibits breast cancer growth

Cytoprotective Effects of KIOM-79 on Streptozotocin Induced Cell Damage by Inhibiting ERK and AP-1

Retinoic acid regulates C/EBP homologous protein expression (CHOP), which negatively regulates myeloid target genes

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