Date of Award

12-1-2012

Degree Type

Dissertation

University or Center

Clark Atlanta University(CAU)

School

School of Arts and Sciences

Degree Name

Ph.D.

Department

Biology

First Advisor

Dr. Shafiq Khan

Second Advisor

Dr. Jaideep Chaudhary

Third Advisor

Dr. Cimona Hinton

Abstract

In prostate cancer cells, 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 (Id 1- 1d4) are dominant negative regulators and bHLH transcription factors and in general promote proliferation, and inhibit differentiation. In the present study, we have investigated the role of Idi and Id3 proteins in the growth inhibitory effects of TGFβ on prostate cancer cells. The effect of TGF β on proliferation and Idl and Id3 expression were investigated in PZ-HPV7, DU145, and PC3 cells. Idi silencing through siRNA was also used in DU145 and PC3 cells to examine its role in anti-proliferative and migratory effects of TGFβ . TGFβ increased expression of Idi and Id3 in all cell lines followed by a later down regulation of Idi in PZ-HPV7 expression and DU145 cells but not in PC3 cells. Id3 expression remained elevated in all three cell lines. This loss of Idi 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 TGFβ 1 induced migration in PC3 cells. These findings suggest an essential role of Id1 and Id3 in TGFβ 1 effects on proliferation and migration in prostate cancer cells.

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