Induction of a variety of preneoplasias and tumours in the mammary glands of transgenic rats.
Although transgenic mouse models for breast cancer have frequently been reported in the literature, transgenic rat models have not been described. We have generated transgenic rats overexpressing the human transforming growth factor alpha (TGF alpha) and c-erbB-2 genes in the mammary gland under the control of the mouse mammary tumour virus (MMTV) long terminal repeat promoter, and have analysed multiple lines of these rats to the second (F2) generation. Female MMTV/TGF alpha rats frequently develop severe hyperplasias during pregnancy, and a variety of tumours of long latency. The mammary glands of MMTV/TGF alpha rats fail to involute fully after the completion of lactation. Expression of the TGF alpha transgene is highest in the hyperplasias. MMTV/c-erbB-2 female rats develop a spectrum of benign and malignant lesions, including ductal carcinoma in situ and carcinomas. Expression of the c-erbB-2 transgene is found in benign tumours such as fibroadenomas, but is highest in the carcinomas. These animals model a spectrum of lesions found in human breasts and suggest that TGF alpha overexpression can act at a relatively early stage in the pathogenesis of breast cancer in the rat, resulting in a predominantly hyperplastic response, whereas overexpression of c-erbB-2 plays a role in the induction of various benign lesions and more advanced breast carcinomas.
Davies
B R
BR
Department of Pathology, Addenbrookes Hospital, University of Cambridge, U.K.
Warren
J R
JR
Schmidt
G
G
Rudland
P S
PS
D000818:Animals; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D016211:Transforming Growth Factor alpha / Q000235:genetics
D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha