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Zinc regulates NF κ B and AP1 transcription factors in prostate cancer cells
Author(s) -
Zou Jing,
Costello Leslie C.,
Franklin Renty B.
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1098-b
Nuclear Factor Kappa B ( N FκB) and Activator Protein 1 (AP1) are nuclear transcription factors that regulate the expression of genes that play a role in tumor growth, angiogenesis and cancer metastasis. Intracellular zinc appears to suppress tumorigenesis in the prostate and to induce apoptosis in prostate cell lines, thus we investigated the effect of zinc signaling on the activation of NFκB and AP1 in prostate cancer cells. PC‐3 cells were treated with ZnCl plus sodium pyrithione to increase intracellular zinc levels. Cells were collected, lysates prepared and the levels of specific proteins analyzed by Western blot. The results showed that Zn stimulated the translocation of NFκB from the cytosol to the nucleus. In addition, the level of cytosolic IκBα was decreased. Zinc also increased the level of phosphorylated cJun present in the nuclear fraction. To determine whether zinc had any effect on molecules involved in metastasis, we also determined the level of MMPs in the cells. Zinc treatment decreased the expression of MMP2. All of the effects of Zn were reversed by the addition of a cell permeable Zn chelator. These results suggest that zinc signals the nuclear translocation and activation of NFκB and AP1. Moreover, the mechanisms of activation likely involve zinc induced loss of the inhibitor IκBα and phosphorylation of cJun respectively. Supported by NIH grant CA079903.