Synergistic effect of cyclin D1 and c-Myc leads to more aggressive and invasive mammary tumors in severe combined immunodeficient mice.
Cyclin D1 is one of the most commonly overexpressed oncogenes in breast cancer; yet, it is not clear whether cyclin D1 alone is capable of causing malignant transformation of mammary epithelial cells. Here, we show that ectopic expression of cyclin D1 in benign mouse mammary epithelial cells promotes cell proliferation, anchorage-independent growth in soft agar, and tumorigenesis in severe combined immunodeficient mice. To address the possible interaction of cyclin D1 and c-myc in malignant transformation, we used cyclin D1/c-myc dual-expressing clones, which displayed more aggressive and invasive phenotype than cyclin D1-expressing clones. These data provide evidence that overexpression of cyclin D1 or coexpression with c-myc could cause invasive malignant transformation of benign mouse mammary epithelial cells. Furthermore, microarray analysis of cyclin D1 and cyclin D1/c-myc clones showed that these two tumor-producing clones might use distinct invasive pathways. In summary, overexpression of cyclin D1 may commit mammary epithelia to a tumor-prone phenotype in which cooperation with other genes, such as synergy with c-myc, may lead to a more aggressive phenotype.
Wang
Yong
Y
Department of Pathology, Barbara Ann Karmanos Cancer Institute, Hudson Webber Cancer Research Center, Wayne State University School of Medicine, Detroit, MI, USA.
Thakur
Archana
A
Sun
Yuan
Y
Wu
Jack
J
Biliran
Hector
H
Bollig
Aliccia
A
Liao
D Joshua
DJ
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
D016271:Proto-Oncogene Proteins c-myc; D019938:Cyclin D1