Findings In Prostate Cancer Reported From Northwestern University

NewsRx.com

October 1, 2009

According to recent research from the United States, "Dietary intake of genistein by patients with prostate cancer has been associated with decreased metastasis and mortality. Genistein blocks activation of p38 mitogen-activated protein kinase and thus inhibits matrix metalloproteinase-2 (MMP-2) expression and cell invasion in cultured cells and inhibits metastasis of human prostate cancer cells in mice."

"We investigated the target for genistein in prostate cancer cells. Prostate cell lines PC3-M, PC3, 1532NPTX, 1542NPTX, 1532CPTX, and 1542CPTX were used. All cell lines were transiently transfected with a constitutively active mitogen-activated protein kinase kinase 4 (MEK4) expression vector (to increase MEK4 expression), small interfering RNA against MEK4 (to decrease MEK4 expression), or corresponding control constructs. Cell invasion was assessed by a Boyden chamber assay. Gene expression was assessed by a quantitative reverse transcription-polymerase chain reaction. Protein expression was assessed by Western blot analysis. Modeller and AutoDock programs were used for modeling of the structure of MEK4 protein and ligand docking, respectively. MMP-2 transcript levels were assessed in normal prostate epithelial cells from 24 patients with prostate cancer from a phase II randomized trial comparing genistein treatment with no treatment. Statistical significance required a P value of .050 or less. All statistical tests were two-sided. Overexpression of MEK4 increased MMP-2 expression and cell invasion in all six cell lines. Decreased MEK4 expression had the opposite effects. Modeling showed that genistein bound to the active site of MEK4. Genistein inhibited MEK4 kinase activity with a half maximal inhibitory concentration of 0.40 mc M (95% confidence interval [CI] = 0.36 to 0.45 mc M). The MMP-2 transcript level in normal prostate epithelial cells was statistically significantly higher in the untreated group (100%) than in the genistein-treated group (24%; difference = 76%, 95% CI = 38% to 115%; P = .045). We identified MEK4 as a proinvasion protein in six human prostate cancer cell lines and the target for genistein," wrote L. Xu and colleagues, Northwestern University (see also Prostate Cancer).

The researchers concluded: "We showed, to our knowledge for the first time, that genistein treatment, compared with no treatment, was associated with decreased levels of MMP-2 transcripts in normal prostate cells from prostate cancer-containing tissue."

Xu and colleagues published their study in the Journal of the National Cancer Institute (MEK4 Function, Genistein Treatment, and Invasion of Human Prostate Cancer Cells. Journal of the National Cancer Institute, 2009;101(16):1141-1155).

For additional information, contact R.C. Bergan, Northwestern University, Dept. of Medical, Robert H Lurie Cancer Center, Olson 8321, 710 N Fairbanks, Chicago, IL 60610, USA.

Publisher contact information for the Journal of the National Cancer Institute is: Oxford University Press Inc., Journals Dept., 2001 Evans Rd., Cary, NC 27513, USA.

Copyright 2009, Proteomics Weekly via NewsRx.com