Understanding the Expression of Two Divergent Cell Growth-Regulated Genes, Cd82 and Minichromosome Maintenance 5, in the Human Prostate

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

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
StatusFinished
Effective start/end date01/08/1131/07/12

Keywords

  • KAI1
  • MCM5
  • cell proliferation
  • prostate
  • gene regulation

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