Prostate Cancer Research with Transgenic Mouse Model

Prostate cancer is the cancer developed in the male reproductive system. The cancer cells can spread from the prostate to other parts of the body, such as the bones and lymph nodes. According to the past statistics, prostate cancer will likely claim more than thirty thousand lives of men in the United States each year, and some more men will be diagnosed with the disease. To date, it is believed that the primary risk factors are obesity, age and family history, but a comprehensive understanding of the causes of prostate cancer remains elusive.

 

 Progress towards the investigation of prostate cancer has been slow due to the lack of suitable animal models that can adequately reproduce the spectrum of benign, latent, aggressive, and metastatic forms of the human diseases, helping studying the spectrum of this uniquely human disease. Although naturally occurring prostatic disease has been reported in some animal's species, such as canine and rodent animals, these animals still fail to provide the appropriate models to adequately study the molecular mechanisms related to the early development and progression of human prostate cancer.

 

 Researchers have started a research program to establish transgenic mouse model for prostate cancer by using a prostate-specific transgenic expression system that has been developed in their laboratories based on the rat probasin (rPB)-encoding gene. To develop an animal model for prostate cancer, they generate several lines of transgenic mice by using the prostate-specific rat probasin promoter to drive expression of the simian virus 40 large tumor antigencoding region. According to their observation, mice express high levels of the transgene and display progressive forms of prostatic disease that histologically resemble human prostate cancer. And prostate tumors have been successfully detected in the mice prostate as early as 10 weeks of age. The immunohistochemical analysis of tumor tissue has demonstrated that dorsolateral prostate-specific secretory proteins are confined to well differentiate ductal epithelial cells adjacent to, or within tumor mass. What's more, the prostate tumors in the mice also display elevated levels of nuclear p53 and a decreased heterogeneous pattern of androgen-receptor expression, as observed in advanced human prostate cancer.

 

The simian virus 40 (SV40) early-region tumor antigens with the ability to induce transformation in vivo have also been used to facilitate this study. The SV40 large tumor T antigen acts as an oncoprote in through interactions with the retinoblastoma and p53 tumor-suppressor gene products, and the small tantigen interacts with a protein phosphatase. They have been used successfully in transgenic mice to induce a transformed state in a variety of systems, including pancreas, mammary gland, and others. It is believed that the directly expressing SV40 tumor antigen in the prostate epithelium of transgenic mice may provide a better mouse model for the development and progression of prostate cancer.

According to their recent study, the rPB gene encodes an androgen- and zinc-regulated protein specific to the dorsolateral epithelium (6-8) and isolation of the rPB gene has facilitated identification of cis-acting androgen-response regions within the 5' flanking region. The ability of the prostate-specific rPB gene promoter to target heterologous genes specifically to the prostate in transgenic mice has been demonstrated. The minimal rPB promoter is specifically regulated by androgens in vivo with the ability to target developmentally and hormonally regulated expression of a heterologous gene specifically to the prostate in transgenic mice. And it has been used to target expression of the SV40 early-region genes specifically to the prostate of transgenic mice.

Nowadays, the establishment of breeding lines of transgenic mice provides an animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer. The ability to induce prostatic disease in a transgenic mouse provides an animal model system to better study prostate cancer and the treatment and prevention of prostate cancer. By the way, the US-based bio-tech service company Creative Animodel, as a professional animal model service supplier, can help develop high quality transgenic mouse models for research use.

Source : Prostate Cancer Treatment in India