Changes in Cyclin Dependent Kinase Inhibitors p21 and p27 during the Castration Induced Regression of Prostatic Adenocarcinoma
The expression of the cyclin dependent kinase inhibitors p21 and p27 was examined in prostatic adenocarcinomas following castration.
Materials and Methods
Male nude mice inoculated with the androgen dependent human prostatic tumor CWR22 were castrated when the tumors reached a volume of 0.8 to 1.1 cm.3 and were sacrificed at 3, 7, 21, 28 and 42 days post-castration. An additional group of mice received a subcutaneous testosterone pellet at 21 days post-castration and was sacrificed at 28 days post-castration. The expression of the Ki-67 antigen, p21 and p27 was examined by immunohistochemistry.
The mitotic rate as well as the number of Ki-67 antigen positive cells decreased to 3% of intact control values by 7 days post-castration and were less than 0.01% of intact control values at 21, 28 and 42 days post-castration. The percentage of p21 expressing cells decreased from 15 +/− 2% in intact controls to less than 1% by 42 days post-castration. In contrast, the percentage of cells that expressed p27 increased from 25 +/− 3% in intact controls to 51 +/− 8% at 3 days post-castration and to 80 to 95% at days, 7, 21, 28 and 42 days post-castration. Testosterone treatment from 21 to 28 days post-castration resulted in an increase in Ki-67 antigen positive cells to 200% of intact controls and a concomitant reduction in p27 expressing cells to about 50% of intact controls. Castration-induced changes in p27 expression were not observed in the CWR22R tumor, a transplantable relapsed derivative of the CWR22 tumor.
Russell B. Meyers, Denise K. Oelschlager, Patricia N. Coan, Andra R. Frost, Heidi L. Weiss, Upender Manne, Thomas G. Pretlow, and William E. Grizzle. "Changes in Cyclin Dependent Kinase Inhibitors p21 and p27 during the Castration Induced Regression of Prostatic Adenocarcinoma" The Journal of Urology 161.3 (1999): 945-949.