Project #3 has been designed to test the hypothesis that the invasive potential of human prostate cancer is determined in part by the relative expression levels of one or several members of the metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) gene families. We have shown that two MMPs, MMP-7 or PUMP-1 and type IV collagenase are overexpressed in primary prostate adenocarcinoma compared to normal prostate. The primary focus in this project will be on the MMP-7 and the TIMP genes. The following specific aims have been designed to test this hypothesis: 1) to characterize the MMP-7 gene in terms of structure, chromosomal localization and transcriptional regulation 2) determine whether the overexpression of MMP-7 in a tumorigenic but weakly invasive and non-metastatic human prostate carcinoma cell line, DU-145, will increase the invasive or metastatic potential when the tumor cells are injected 1.p. or orothotopically into severe combined immuno-deficient (SCID) mice. 3) determine at the levels of messenger RNA and protein the expression of the TIMP 1 and 2 genes in cultured DU-145 and PC-3 human prostate carcinoma cells. 4) determine whether the overexpression of the TIMP 1 gene in a tumorigenic and highly invasive human prostate carcinoma cell line, PC-3, which expressed type I collagenase and invades skeletal muscle when injected 1.p. into SCID mice reduces the invasive behavior of the cell line. the proposed work in this Project will complement the human tissue studies to be carried out in Project #1 and the proposed studies related to the functional role of integrins in prostate tumor cell invasion proposed in Project #2. This Project will utilize both of the Core Projects including the SCID mouse and microscopy cores.
| Nagle, Raymond B; Algotar, Amit M; Cortez, Connie C et al. (2013) ERG overexpression and PTEN status predict capsular penetration in prostate carcinoma. Prostate 73:1233-40 |
| Sroka, Isis C; Sandoval, Cynthia P; Chopra, Harsharon et al. (2011) Macrophage-dependent cleavage of the laminin receptor ?6?1 in prostate cancer. Mol Cancer Res 9:1319-28 |
| Sroka, Isis C; Anderson, Todd A; McDaniel, Kathy M et al. (2010) The laminin binding integrin alpha6beta1 in prostate cancer perineural invasion. J Cell Physiol 224:283-8 |
| Sroka, Isis C; Pond, Gerald D; Nagle, Raymond B et al. (2009) Human Cell Surface Receptors as Molecular Imaging Candidates for Metastatic Prostate Cancer. Open Prost Cancer J 2:59-66 |
| Ports, Michael O; Nagle, Ray B; Pond, Gerald D et al. (2009) Extracellular engagement of alpha6 integrin inhibited urokinase-type plasminogen activator-mediated cleavage and delayed human prostate bone metastasis. Cancer Res 69:5007-14 |
| Demetriou, Manolis C; Kwei, Kevin A; Powell, Marianne B et al. (2008) Integrin A6 Cleavage in Mouse Skin Tumors. Open Cancer J 2:1-4 |
| Sroka, Isis C; Chen, Man Ling; Cress, Anne E (2008) Simplified purification procedure of laminin-332 and laminin-511 from human cell lines. Biochem Biophys Res Commun 375:410-3 |
| Moran, Carlos M; Garriock, Robert J; Miller, Melanie K et al. (2008) Expression of the fast twitch troponin complex, fTnT, fTnI and fTnC, in vascular smooth muscle. Cell Motil Cytoskeleton 65:652-61 |
| King, Tamara E; Pawar, Sangita C; Majuta, Lisa et al. (2008) The role of alpha 6 integrin in prostate cancer migration and bone pain in a novel xenograft model. PLoS One 3:e3535 |
| Demetriou, Manolis C; Stylianou, Panayiota; Andreou, Maria et al. (2008) Spatially and temporally regulated alpha6 integrin cleavage during Xenopus laevis development. Biochem Biophys Res Commun 366:779-85 |
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