PubMed Health⌕ Search

Biomedical subjects

G A Henderson

Publications and source records attributed to G A Henderson.

5 recordsLinked to original sources
PubMed1997

Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells.

Prostate-specific antigen (PSA) is a widely used marker for the diagnosis and management of prostate cancer. Minimal enhancer/promoter constructs derived from the 5' flank of the human PSA gene (prostate-specific enhancer) were inserted into adenovirus type 5 DNA so as to drive the E1A gene, thereby creating a prostate-specific enhancer-containing virus, CN706. E1A was expressed at high levels in CN706-infected human PSA-producing LNCaP cells but not in CN706-infected DU145 cells, which are human prostate cells that do not express PSA. The titer of CN706 was significantly higher in LNCaP cells compared to several human cell lines that do not produce PSA (HBL100, PANC-1, MCF-7, DU145, and OVCAR3). Furthermore, in LNCaP cells, the yield of CN706 was dependent on exogenous androgen (R1881). CN706 destroyed large LNCaP tumors (1 x 10(9) cells) and abolished PSA production in nu/nu mouse xenograft models with a single intratumoral injection.

Adenovirus E1A Proteins↗
PubMed1996

Prostate-specific antigen expression is regulated by an upstream enhancer.

Prostate cancer can be detected using assays for blood-borne prostate-specific antigen (PSA), which is the clinically most useful diagnostic marker of malignant disease. This paper characterizes the 5 -flanking prostate-specific enhancer which controls expression of the human PSA gene This enhancer, located between -5824 and -3738, is androgen-responsive and requires a promoter for activity. Inductions of 12-100-fold activity occur at 1 nM concentrations of the testosterone analog R1881. The enhancer demonstrated tissue specificity as judged by transfections of several human cell lines. Electrophoretic mobility shift assays comparing nuclear extracts from breast cancer cells MCF-7, and prostate cancer cells LNCaP, showed three regions of prostate-specific binding. These three regions are -4168 to -4797 (region I), -4710 to 4479 (region II), and -4168 to -3801 (region III). Region III contained a putative androgen response element at -4136 that markedly affected activity if mutated. These data suggest that prostate-specific gene expression may involve interaction of prostate-specific proteins or protein complexes with the enhancer in addition to binding of the androgen receptor to androgen response elements.

Androgens↗