SV40 T-antigen induces breast cancer formation with a high efficiency in lactating and virgin WAP-SV-T transgenic animals but with a low efficiency in ovariectomized animals.
The whey acid protein (WAP) is a major mouse milk protein and its gene expression is induced by various lactotrophic hormones (eg, estrogen, progesterone). Transgenic animals harboring the early SV40 coding region (T/t-antigen) under the transcriptional control of the WAP promoter develop breast cancer after the first lactation period. The tumor cells synthesize the SV40 T-antigen with a high efficiency indicating that WAP-SV-T expression escapes down-regulation after the lactation period. However about 5-10% of the tumors became T-antigen negative during tumor progression and WAP-SV-T expression was only demonstrable by PCR analysis. Both T-antigen positive and negative tumor cells expressed the estrogen and progesterone receptor at a comparable rate, indicating that hormone receptor levels do not determine expression of the WAP-SV-T transgene. Furthermore, WAP and WAP-SV-T gene expression are not restricted to the pregnancy-lactation period. Virgin animals also express both genes with a low efficiency and about 70% of these animals also developed T-antigen positive breast tumors. The tumor rate however was strongly reduced in ovariectomized animals, indicating that the ovary hormones play a critical role in breast cancer formation.
Santarelli
R
R
Institut für Molekularbiologie und Biochemie, Freien Universität Berlin, Germany.
Tzeng
Y J
YJ
Zimmermann
C
C
Guhl
E
E
Graessmann
A
A
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D015870:Gene Expression; D007774:Lactation; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D010052:Ovariectomy; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013539:Simian virus 40 / Q000235:genetics
D000952:Antigens, Polyomavirus Transforming; D017931:DNA Primers; D008894:Milk Proteins; D011993:Recombinant Fusion Proteins; C024471:whey acidic proteins