Transgenic mouse with human mutant p53 expression in the prostate epithelium

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Apoptosis is frequently disrupted in prostate tumor cells, promoting cancer cell survival.
• The p53 protein is a key regulator of cancer progression, partly through its role in inducing apoptosis.
• Understanding p53's role in prostate cancer requires appropriate preclinical models.

Purpose of the Study:

• To generate a novel transgenic mouse model expressing mutant p53 specifically in the prostate.
• To investigate the effects of mutant p53 accumulation on prostate tissue and apoptotic function.

Main Methods:

• Generation of transgenic mice using a construct with the rat probasin promoter and a mutant human p53 fragment.
• Confirmation of transgene incorporation via Southern analysis.
• Assessment of mutant p53 protein expression using immunofluorescence and apoptosis using the TUNEL method.

Main Results:

• Successful generation of transgenic mice with confirmed transgene integration and nuclear accumulation of mutant p53 in the prostate.
• Development of prostatic intraepithelial neoplasia (PIN) III and IV in the prostate of 52-week-old transgenic mice.
• Demonstrated reduction in the prostate's apoptotic capacity following castration in transgenic mice compared to controls.

Conclusions:

• The developed transgenic rPB-mutant p53 mouse model exhibits prostate neoplastic lesions and impaired apoptosis.
• This model is valuable for studying the interplay of genes in prostate tumor progression.
• Future studies can utilize this model to explore the transition from slow-growing tumors to metastatic cancer.