Abstract：
:A chimeric CYCLIN D1-TROP2 mRNA was isolated from human ovarian and mammary cancer cells. The CYCLIN D1-TROP2 mRNA was shown to be a potent oncogene as it transforms naïve, primary cells in vitro and induces aggressive tumor growth in vivo in cooperation with activated RAS. Silencing of the chimeric mRNA inhibits the growth of breast cancer cells. The CYCLIN D1-TROP2 mRNA was expressed by a large fraction of the human gastrointestinal, ovarian, and endometrial tumors analyzed. It is most frequently detected in intestinal cell aneuploid cancers and it is coexpressed with activated RAS oncogenes, consistent with a cooperative transforming activity in human cancers. The chimeric mRNA is a bicistronic transcript of post transcriptional origin that independently translates the Cyclin D1 and Trop-2 proteins. This is a novel mechanism of CYCLIN D1 activation that achieves the truncation of the CYCLIN D1 mRNA in the absence of chromosomal rearrangements. This leads to a higher CYCLIN D1 mRNA stability, with inappropriate expression during the cell cycle. The stabilized CYCLIN D1 mRNA cooperates with TROP2 in stimulating the growth of the expressing cells. These findings show a novel epigenetic, oncogenic mechanism, which seems to be widespread in human cancers.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Guerra E,Trerotola M,Dell' Arciprete R,Bonasera V,Palombo B,El-Sewedy T,Ciccimarra T,Crescenzi C,Lorenzini F,Rossi C,Vacca G,Lattanzio R,Piantelli M,Alberti Sdoi
10.1158/0008-5472.CAN-07-6135subject
Has Abstractpub_date
2008-10-01 00:00:00pages
8113-21issue
19eissn
0008-5472issn
1538-7445pii
68/19/8113journal_volume
68pub_type
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