Abstract
We have previously described hTDE1, the human homologue of the recently described TDE1/TMS family of proteins whose members have been identified in several species. Although a defined biochemical activity has yet to be assigned to TDE1/TMS family members, previous results point to the overexpression of family members in tumor cell lines or tissues. To define whether hTDE1 may directly impact on neoplastic transformation, we derived and characterized stable Rat-1 transfectants that constitutively express hTDE1 at the plasma membrane. Expression of hTDE1 in Rat-1 transfectants had a significant effect on cell contact inhibition in vitro as judged by a focus formation assay. In addition, by monitoring caspase-3 activity and Hoechst staining, we determined that hTDE1 overexpression partially protects cells from serum starvation- and etoposide-induced apoptosis. Finally, hTDE1 Rat-1-expressing clones accelerated the formation of tumors in a nude mouse assay. Our results suggest that hTDE1 contributes directly to oncogenesis in vivo that may in part be explained by its effect on apoptosis in vitro.
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Acknowledgements
We thank Jason Madore for technical assistance, and Wissal El-Assaad and Abdellah Belmaaza for stimulating discussions. This research was funded in part by a Canadian Institute of Health Research (CIHR) grant and a Cancer Research Society grant to A-MM-M MB has been supported by a CIHR studentship as well as awards from the Canderel and Marc-Bourgie funds of the Institut du cancer de Montréal. FV was the recipient of a Canderel studentship award. A-MM-M is the recipient of a Fonds de la recherche en santé au Québec (FRSQ) Chercheur National Fellowship. RB is the recipient of an FRSQ Senior Fellowship.
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Bossolasco, M., Veillette, F., Bertrand, R. et al. Human TDE1, a TDE1/TMS family member, inhibits apoptosis in vitro and stimulates in vivo tumorigenesis. Oncogene 25, 4549–4558 (2006). https://doi.org/10.1038/sj.onc.1209488
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DOI: https://doi.org/10.1038/sj.onc.1209488
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