Prostatic dysplasia associated with increased expression of c-myc in neonatally estrogenized mice.
Neonatal estrogenization of the mouse with diethylstilbestrol (DES; 2 micrograms./pup/day for days 1 to 3) or 17 beta-estradiol (200 micrograms./pup/day for days 1 to 3) resulted in epithelial dysplasia in the posterior periurethral region of the prostate at the age of 1 year. The dysplastic lesions ranged from mild to severe and, in addition to emergence of nuclear anaplasia, the architectural pattern of the glands was disturbed. Prenatal estrogenization (100 micrograms./kg. of maternal body weight on days 13 and 15 of gestation) only resulted in mild epithelial hyperplasia and occasional dysplasia in the ventral lobe of the prostate, but not in the posterior periurethral region. When neonatally estrogenized mice were allowed to grow until the age of 18 months, the degree and extent of the dysplasia of the posterior periurethral region was increased, but no frank invasion or metastases could be demonstrated. Combined estrogen and androgen treatment of neonatally estrogenized mice for 3 months (between 9 and 12 months of age) augmented nuclear dysplasia, but no invasive growth was seen in this group, either. Mild epithelial dysplasia 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, Northern blot analysis of total RNAs showed that the levels of c-myc mRNA were increased in the ventral and dorsolateral lobes, coagulating glands and prostatic urethra of neoDES mice at the age of 9 months. However, it remains to be determined whether the increase in c-myc expression is involved in the development of hyperplastic and dysplastic changes in the prostate of neoDES mice.
Pylkkänen
L
L
Department of Anatomy, University of Turku, Finland.
Mäkelä
S
S
Valve
E
E
Härkönen
P
P
Toikkanen
S
S
Santti
R
R
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D004054:Diethylstilbestrol / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics*; D008297:Male; D051379:Mice; D011467:Prostate / Q000187:drug effects / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D004054:Diethylstilbestrol