This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Matrix metalloproteinases (MMPs) are promising targets for cancer therapy. However, recent clinical trials of MMP inhibitors have been disappointing. Certain MMPs may regulate apoptosis signaling pathways and sensitize tumor cells to apoptotic signals. Inhibition of these MMPs will promote tumor cell survival and this effect may offset the beneficial activity in inhibition of metastasis. Matrix metalloproteinase-9 (MMP-9) expression is significantly increased in malignant prostate cancers. In addition to its ability to cleave collagens and basement membrane components, MMP-9 also cleaves and activates the multifunctional cytokine TGF-?. TGF-? (having three isoforms in mammals: TGF-?1, ?2, ?3) is an important regulator of normal and malignant prostate. While TGF-?1 induces apoptosis in certain prostate cancer cells, TGF-?2 blocks apoptosis. By activating all three isoforms of TGF-?, MMP-9 may have different net effect on prostate cancer apoptosis depending on the status of expression of TGF-? isoforms, their receptors, and the downstream signaling molecules. There is a critical need to determine the effects of MMP-9 on apoptosis in prostate cancer. Presumable, inhibition of MMP-9 will be beneficial in patients where MMP-9-mediated TGF-? activation has an anti-apoptotic effect in cancer cells. Selection of appropriate patients according to the status of TGF-? signaling machinery may be critical for future clinical trials to evaluate the therapeutic efficacy of MMP-9 inhibitors. The objective of this research is to define the role of MMP-9 in prostate cancer apoptosis and how the effects of MMP-9 on apoptosis change along with prostate cancer progression. At the completion of this project, we expect to clarify the role of MMP-9 in apoptosis regulation in prostate cancer and how this role may change in relation with the changes of TGF-? signaling at different stages of prostate cancer progression.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-RI-5 (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
North Dakota State University
Schools of Arts and Sciences
United States
Zip Code
Lundquist, Taylor A; Kittilson, Jeffrey D; Ahsan, Rubina et al. (2018) The effect of within-instar development on tracheal diameter and hypoxia-inducible factors ? and ? in the tobacco hornworm, Manduca sexta. J Insect Physiol 106:199-208
Jensen, Jaime L; Wu, Qiong; Colbert, Christopher L (2018) NMR assignments of the N-terminal signaling domain of the TonB-dependent outer membrane transducer PupB. Biomol NMR Assign 12:91-94
Edwinson, Adam; Widmer, Giovanni; McEvoy, John (2016) Glycoproteins and Gal-GalNAc cause Cryptosporidium to switch from an invasive sporozoite to a replicative trophozoite. Int J Parasitol 46:67-74
Holubová, Nikola; Sak, Bohumil; Hor?i?ková, Michaela et al. (2016) Cryptosporidium avium n. sp. (Apicomplexa: Cryptosporidiidae) in birds. Parasitol Res 115:2243-51
Linder, Douglas P; Rodgers, Kenton R (2015) Methanethiol Binding Strengths and Deprotonation Energies in Zn(II)-Imidazole Complexes from M05-2X and MP2 Theories: Coordination Number and Geometry Influences Relevant to Zinc Enzymes. J Phys Chem B 119:12182-92
Jensen, Jaime L; Balbo, Andrea; Neau, David B et al. (2015) Mechanistic Implications of the Unique Structural Features and Dimerization of the Cytoplasmic Domain of the Pseudomonas Sigma Regulator, PupR. Biochemistry 54:5867-77
Ghospurkar, Padmaja L; Wilson, Timothy M; Liu, Shengqin et al. (2015) Phosphorylation and cellular function of the human Rpa2 N-terminus in the budding yeast Saccharomyces cerevisiae. Exp Cell Res 331:183-99
Piya, Gunjan; Mueller, Erica N; Haas, Heather K et al. (2015) Characterization of the interaction between Rfa1 and Rad24 in Saccharomyces cerevisiae. PLoS One 10:e0116512
Jensen, Jaime L; Indurthi, Venkata S K; Neau, David B et al. (2015) Structural insights into the binding of the human receptor for advanced glycation end products (RAGE) by S100B, as revealed by an S100B-RAGE-derived peptide complex. Acta Crystallogr D Biol Crystallogr 71:1176-83
Singh, Raushan K; Cho, Kyongshin; Padi, Satish K R et al. (2015) Mechanism of N-Acylthiourea-mediated activation of human histone deacetylase 8 (HDAC8) at molecular and cellular levels. J Biol Chem 290:6607-19

Showing the most recent 10 out of 141 publications