A role for polyploidy in the tumorigenicity of Pim-1-expressing human prostate and mammary epithelial cells.
BACKGROUND
Polyploidy is a prominent feature of many human cancers, and it has long been hypothesized that polyploidy may contribute to tumorigenesis by promoting genomic instability. In this study, we investigated whether polyploidy per se induced by a relevant oncogene can promote genomic instability and tumorigenicity in human epithelial cells.


RESULTS
When the oncogenic serine-threonine kinase Pim-1 is overexpressed in immortalized, non-tumorigenic human prostate and mammary epithelial cells, these cells gradually converted to polyploidy and became tumorigenic. To assess the contribution of polyploidy to tumorigenicity, we obtained sorted, matched populations of diploid and polyploid cells expressing equivalent levels of the Pim-1 protein. Spectral karyotyping revealed evidence of emerging numerical and structural chromosomal abnormalities in polyploid cells, supporting the proposition that polyploidy promotes chromosomal instability. Polyploid cells displayed an intact p53/p21 pathway, indicating that the viability of polyploid cells in this system is not dependent on the inactivation of the p53 signaling pathway. Remarkably, only the sorted polyploid cells were tumorigenic in vitro and in vivo.


CONCLUSIONS
Our results support the notion that polyploidy can promote chromosomal instability and the initiation of tumorigenesis in human epithelial cells.
Roh
Meejeon
M
Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
Franco
Omar E
OE
Hayward
Simon W
SW
van der Meer
Riet
R
Abdulkadir
Sarki A
SA
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D042822:Genomic Instability; D006801:Humans; D008297:Male; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011123:Polyploidy; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019098:Telomerase / Q000378:metabolism
C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1; D019098:Telomerase