Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice.
Physical associations between cyclins, viral oncogenes and tumour suppressor genes imply a central role for cyclins in growth control. Cyclin D1 was identified as a candidate oncogene (PRAD1) in tumour-specific DNA rearrangements and is suspected to be a contributor to several types of neoplasms including breast cancer. Cyclin D1 also rescues G1 cyclin-defective Saccharomyces cerevisiae, and is a growth-regulated gene. Despite evidence suggesting that cyclin D1 is an oncogene, its ability to transform cells directly in culture remains controversial. To evaluate its potential to deregulate growth in vivo in a physiologically relevant tissue we overexpressed cyclin D1 in mammary cells in transgenic mice. We report here that overexpression of cyclin D1 resulted in abnormal mammary cell proliferation including the development of mammary adenocarcinomas. We conclude that overexpression of cyclin D1 deregulates cell proliferation and can induce tumorigenic changes in mammary tissues, suggesting that cyclin D1 indeed plays an important oncogenic role in breast cancer.
Wang
T C
TC
Department of Medicine, Massachusetts General Hospital, Boston 02114.
Cardiff
R D
RD
Zukerberg
L
L
Lees
E
E
Arnold
A
A
Schmidt
E V
EV
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000235:genetics; D008297:Male; D008321:Mammary Glands, Animal / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D009857:Oncogenes; D014407:Tumor Cells, Cultured
D016213:Cyclins; D015513:Oncogene Proteins; D019938:Cyclin D1