Project Details
Abstract
The MCM5 is one of the MCM family genes. The MCM proteins are replication
initiation factors and have been regarded as biological marker of dysplasia
and malignancy. Previous report has indicated that patients with prostate
cancer had higher levels of MCM5 in their urine sediments than men without
malignancy; however, the regulatory mechanisms of MCM5 gene in the prostate
are still unknown. The CD82 gene, which is also denoted as KAI1, belongs to
a transmembrane 4 superfamily. CD82/KAI1 has been regarded as the metastasis
suppressor gene in prostate cancer in previous reports. Our studies using RT-PCR
and immunoblot assays indicated that gene expression of MCM5 and CD82/KAI1 are
contrary in the human prostatic carcinoma cells and are relative to neoplasia.
The study of this thesis was to understand and characterize the function of
CD82/KAI1 and MCM5 gene in the prostate carcinogenesis. The regulators were
investigated in this studies include bioflavonoids, retinol acid, steroid,
cytokines and anticancer drugs. Transient gene expression assays also found
the contrary characteristics between CD82/KAI1 and MCM5 under the regulation
of p53. Adriamycin treatment in the wild-type p53 expressing LNCaP cells or
transient overexpression of p53 into the null-p53 PC-3 cells upregulated the
promoter activity of CD82/KAI1 gene but downregualted the promoter activity
of MCM5 gene. Other experimental results also revealed that bioflavonoid,
vitamin A, and anticancer drugs such as 17-(allylamino)-17-
demethoxygeldanamycin and paclitaxel enhanced gene expression of CD82/KAI1 or
blocked gene expression MCM5 which attenuated cell proliferation. The long-term
objects of this thesis are to understand the regulatory mechanism of CD82/KAI1
and MCM5 genes in the neoplasia of the prostate, and to employ these concepts
in the early diagnosis, drug screen, and gene therapy of the disease of prostate
carcinoma.
Project IDs
Project ID:PC10001-0099
External Project ID:NSC98-2314-B182A-099-MY3
External Project ID:NSC98-2314-B182A-099-MY3
Status | Finished |
---|---|
Effective start/end date | 01/08/11 → 31/07/12 |
Keywords
- KAI1
- MCM5
- cell proliferation
- prostate
- gene regulation
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