Deregulated estrogen receptor alpha expression in mammary epithelial cells of transgenic mice results in the development of ductal carcinoma in situ.
A conditional tetracycline-responsive transgenic mouse model with deregulated estrogen receptor alpha expression in mammary epithelial cells developed ductal hyperplasia (DH), lobular hyperplasia, and ductal carcinoma in situ (DCIS) by 4 months of age. Higher proliferative rates were found in both normal and abnormal ductal and lobular structures. DH and DCIS but not normal ductal structures showed an increased percentage of cells with nuclear-localized cyclin D1. No differences in either the prevalence or extent of these phenotypes following exogenous 17beta-estradiol treatment were found suggesting that alteration of ERalpha expression was the rate-limiting factor in initiation of DH, lobular hyperplasia, and DCIS.
Frech
M Silvina
MS
Lombardi Comprehensive Cancer Center, Departments of Oncology and Pathology, Georgetown University, 3970 Reservoir Road, Washington, DC 20057, USA.
Halama
Ewa D
ED
Tilli
Maddalena T
MT
Singh
Baljit
B
Gunther
Edward J
EJ
Chodosh
Lewis A
LA
Flaws
Jodi A
JA
Furth
Priscilla A
PA
D000818:Animals; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism*; D044584:Carcinoma, Ductal / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006965:Hyperplasia; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D019938:Cyclin D1; D004958:Estradiol