The Prostate-Specific Antigen (PSA) promoter region (initial 5’ sequence), PSA promoter withenhancer sequence, and the constitutively expressed Phospho Glycerate Kinase (PGK) promoter were cloned into an Ad5 vector system with an intention to compare the efficiencyand specificity of gene expression in Prostate cancer and the control HEK293 cell lines using aGFP reporter gene. The PGK promoter was found to be more efficient compared to the PSA promoter with enhancer region; on the other hand the PSA promoter plus enhancer region wasmore efficient compared to the PSA promoter only. Further studies can be carried out in order to evaluate the specificity and the infectivity of the different types of adenoviral vectors byusing promoters of variable strength.
Prostate cancer is the third most common cause of cancer death in men after lung andcolorectal cancers (1). The conventional strategies for the treatment of metastatic prostatecancers, like chemotherapy, radiation therapy, and hormone therapy can provide onlysymptomatic palliation. On the other hand, gene therapy rather eliminates the cause of thedisease (2). Gene therapy provides the opportunity to selectively introduce genes into cancer cells targeting multiple biological processes including induction of cytotoxic and apoptoticresponses, correction of aberrant cell growth regulation and elicit anti-tumour immuneresponses in the tumour. Despite the initial setbacks due to side effects, the gene therapystrategy has evolved to an efficient approach to cancer treatment by the recent advances indefining the genetic alterations in cancer, in gene regulation, and delivery vectorology (3).The practical advantages and the application potential of the adenoviral vectors have drawn theattention of many scientists in the field of gene therapy. Adenoviral vectors are the potentialcandidates to meet the requirements of the ideal gene delivery vector for cancer treatment for the following reasons: adenoviral vectors are well characterized and thoroughly studied as amodel system for eukaryotic gene regulation, their size (around 36 kilobases) is suitable for development of large-capacity vectors with minimal viral sequence. Adenoviral vectors can beeasily generated and manipulated with good stability and can be produced in high titers (10
plaque-forming units (PFU)/mL). The adenoviral vectors exhibit a broad host range in
with high infectivity in both dividing and quiescent cells, they do not integrateinto the host cell genome and genes thus delivered are expressed episomally with lowgenotoxicity, they exhibit wide variety of routes of administration in different tissue types and,no significant side effects were reported while demonstrating the safety of the adenoviralvectors for gene transfer (4). Here experiments were made with the
most commonly usedadenovirus vector systems, which are based on adenovirus
serotype 5 (Ad5), belonging tospecies C. These have shown promising
oncolytic activity and are being tested in the clinic for antitumor
efficacy (5).Human adenoviruses belong to the family
. They form alarge group comprising 51 different serotypes. These 51 serotypes of human adenoviruses arefurther divided into six different species (designated from A to F) (6, 7). Ad5 from species Chas been the focus of vector development for more than two decades (8).The Ad5 vector used is replication incompetent due to deletions of the E1 and E3 genes. Thesedeletions render the virus replication defective and provide space for large foreign DNA, up to7.5 kb. The E1 gene is required in the viral assembly and is complemented in the adenovirus packaging cell line HEK293. The E3 gene encodes proteins involved in evading host immunityand is dispensable (9).