PROSTATIC DYSPLASIA ASSOCIATED WITH INCREASED EXPRESSION OF C-MYC IN NEONATALLY ESTROGENIZED MICE

Neonatal estrogenization of the mouse with diethylstilbestrol (DES; 2 mug/pup/day for days 1 to 3) or 17beta-estradiol (200 mug./pup/day for days 1 to 3) resulted in epithelial dysplasia in the posterior periur ethral region of the prostate at the age of 1 year. The dysplastic les ions ranged from mild to severe and, in addition to emergence of nucle ar anaplasia, the architectural pattern of the glands was disturbed. P renatal estrogenization (100 mug./kg. of maternal body weight on days 13 and 15 of gestation) only resulted in mild epithelial hyperplasia a nd occasional dysplasia in the ventral lobe of the prostate, but not i n the posterior periurethral region. When neonatally estrogenized mice were allowed to grow until the age of 18 months, the degree and exten t of the dysplasia of the posterior periurethral region was increased, but no frank invasion or metastases could be demonstrated. Combined e strogen and androgen treatment of neonatally estrogenized mice for 3 m onths (between 9 and 12 months of age) augmented nuclear dysplasia, bu t no invasive growth was seen in this group, either. Mild epithelial d ysplasia was found in the dorsolateral lobes and coagulating glands of similarly treated control animals. A relation between the activation of certain proto-oncogenes and the development of several cancers has been shown in humans and experimental animals. In the present study, N orthern blot analysis of total RNAs showed that the levels of c-myc mR NA were increased in the ventral and dorsolateral lobes, coagulating g lands and prostatic urethra of neoDES mice at the age of 9 months. How ever, it remains to be determined whether the increase in c-myc expres sion is involved in the development of hyperplastic and dysplastic cha nges in the prostate of neoDES mice.