CURRENT RESEARCH IN THE DAY LAB |
| ADAM15 Project Synopsis |
| Prostate cancer (PCa) is the second most prevalent cancer
in males worldwide (1). It can be successfully treated earlier
when the cancer is hormone dependent by many methods of which includes
androgen replacement therapy. Unfortunately, hormone independent
prostate cancer is irresponsive to most cancer treatments and has
prevalence to metastasize to secondary sites such as bone, liver
and lung. The process of cancer metastasis involves multiple steps
to allow primary tumors to detach from the original site and migrate
to seed into a secondary site. The metastatic cascade includes
two essential steps in allowing cancerous spread—cell detachment
from the surrounding extracellular matrix and stromal invasion
(2). The matrix metalloproteinase (MMP) family have been implicated
in supporting cancer cell metastasis by remodeling the extracellular
matrix (3). But a recently discovered family of zinc metalloproteinases
known as the ADAM (a disintegrin and metalloproteinase) family
may also contribute to cancer cell metastasis (4). A member of
this family, ADAM 15, was found to be transcriptionally and translationally
upregulated in metastatic prostate cancer patients by our laboratory
(Fig. 1) (5). ADAM 15 is a multi-domain, transmembrane glycoprotein
that also has been implicated in extracellular matrix degradation.
The goal of the Day lab on this project is to investigate the role
ADAM 15 plays within the metastatic progression of prostate cancer. |
| Nrf2 Project Synopsis |
| Studies have indicated that reactive oxygen species (ROS) play
a role in the onset of several age-related diseases including cancer.
Increases in ROS result in oxidative damage to DNA, which leads to
mutations that promote tumorigenesis. A recent study has demonstrated
that ROS damage to DNA is increased in the TRAMP mouse model of prostate
cancer. Nrf2 is a transcription factor that has been demonstrated
to regulate the expression of antioxidant proteins and enzymes, such
as glutathione-s-transferase that detoxify secondary metabolites
of oxidative stress. We have found that Nrf2 is down regulated in
primary prostate tumors. However, it is unknown if the loss of Nrf2
results in mutagenic DNA damage in the prostate gland. |
| DNA Methylation
Project Synopsis |
| DNA methylation is regulated by a family of DNA methyltransferase
enzymes (Dnmt-1, Dnmt-3a and Dnmt-3b). Dnmt-1 has been implicated
in the aberrant methylation of genes in some tumors including prostate
cancer. Specific studies examining Dnmt-1 function in cells has demonstrated
an association of Dnmt-1 and cellular transformation including decreased
contact inhibition, increased genomic methylation, increased growth
in soft agar and increased tumorigenicity. These data suggest that
increased DNA methyltransferase levels and activity affect the methylation
status of genes critical to tumor formation and progression. We have
recently shown that Dnmt-1 is transcriptionally regulated by E2F-1
following the disruption of Rb. We have also shown that prostate
tumorigenesis can be dramatically inhibited by the methyltransferase
inhibitor, 5-aza-2’deoxycytidine (5-aza), in the TRAMP mouse
model of prostate cancer. |
| |
RESEARCH OPPORTUNITIES IN THE DAY LAB |
There are always opportunities for Graduate Student and Post
Doctoral Candidate research in the Day Lab. To inquire further
about a current opportunity contact:
Mark L. Day Lab
Address:
6131 CCGC
1500 E. Medical Center Drive
Ann Arbor , MI 48109
(734) 647-2528 |
