Lindsey Walker

Clark Atlanta University, Atlanta, GA, United States

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Publications (2)7.3 Total impact

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    ABSTRACT: BACKGROUND: In prostate cancer cells, transforming growth factor β (TGFβ) inhibits proliferation in earlier stages of the disease; however, the cancer cells become refractory to growth inhibitory effects in advanced stages where TGFβ promotes cancer progression and metastasis. Inhibitor of differentiation (Id) family of closely related proteins (Id1-Id4) are dominant negative regulators and basic helix loop helix (bHLH) transcription factors and in general promote proliferation, and inhibit differentiation. In the present study, we have investigated the role of Id1 and Id3 proteins in the growth inhibitory effects of TGFβ on prostate cancer cells. METHODS: The effect of TGF β on proliferation and Id1 and Id3 expression were investigated in PZ-HPV7, DU145, and PC3 cells. Id1 silencing through siRNA was also used in DU145 and PC3 cells to examine its role in anti-proliferative and migratory effects of TGFβ. RESULTS: TGFβ increased expression of Id1 and Id3 in all cell lines followed by a later down regulation of Id1 in PZ-HPV7 expression and DU145 cells but not in PC3 cells. Id3 expression remained elevated in all three cell lines. This loss of Id1 protein correlated with an increase of CDKNI p21. Id1 knockdown in both DU145 and PC3 cells resulted in decreased proliferation. However, while TGFβ caused a further decrease in proliferation of DU145, but had no further effects in PC3 cells. Knockdown of Id1 or Id3 inhibited TGFβ1induced migration in PC3 cells. CONCLUSIONS: These findings suggest an essential role of Id1 and Id3 in TGFβ1 effects on proliferation and migration in prostate cancer cells. Prostate © 2012 Wiley Periodicals, Inc.
    The Prostate 10/2012; · 3.84 Impact Factor
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    ABSTRACT: Transforming growth factor-β (TGFβ) is a secreted cytokine implicated as a factor in cancer cell migration and invasion. Previous studies have indicated that TGFβ isoforms may exert differential effects on cancer cells during different stages of the disease, however very little is known about the expression patterns and activity of the three isoforms in prostate cancer. Non-traditional signaling pathways including the PI3-Kinase have been associated with TGFβ-mediated effects on cancer cell invasion. In the present study, we have carried out expression analysis of TGFβ isoforms and signaling components in cell line models representing different stages of prostate cancer and studied the differential effects of specific isoforms on migratory and invasive behavior and induction of the PI3-kinase pathway. TGFβ1 and TGFβ3 were expressed in all cell lines, with TGFβ3 expression increasing in metastatic cell lines. Both TGFβ1 and TGFβ3 induced motility and invasive behavior in PC3 cells, however, TGFβ3 was significantly more potent than TGFβ1. TGFβRI and Smad3 inhibitors blocked TGFβ1 and TGFβ3 induced motility and invasion. TGFβ3 caused a significant increase in pAKT(ser473) in PC3 cells and PI3-kinase inhibitor LY294002 blocked TGFβ3 induced migration, invasion and phosphorylation of AKT. Both TGFβRI and Smad3 inhibitors blocked TGFβ3 induced pAKT(ser473). Based on these results, we conclude that TGFβ3 is expressed in metastatic prostate cancer cell lines and is involved in induction of invasive behavior in these cells. Furthermore, these effects of TGFβ3 are TGFβRI and Smad3 dependent and mediated via the PI3-kinase pathway.
    Clinical and Experimental Metastasis 06/2012; · 3.46 Impact Factor

Publication Stats

8 Citations
7.30 Total Impact Points

Institutions

  • 2012
    • Clark Atlanta University
      • Center for Cancer Research and Therapeutic Development
      Atlanta, GA, United States