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Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA
Nathalie Conte1, Emmanuelle Charafe-Jauffret, Bénédicte Delaval
1Département d'Oncologie Moléculaire, U119 Inserm, 27 Bd. Leï Roure, 13009, Marseille, France.
Abstract:
The three human TACC genes encode a family of proteins that are suspected to play a role in carcinogenesis. Their function is not precisely known; a Xenopus TACC protein called Maskin is involved in translational control, while the Drosophila D-TACC associates with microtubules and centrosomes. We have characterized the human TACC1 gene and its products. The TACC1 gene is located in region p12 of chromosome 8; its mRNA is ubiquitously expressed and encodes a protein with an apparent molecular mass of 125 kDa, which is cytoplasmic and mainly perinuclear. We show that TACC1 mRNA gene expression is down-regulated in various types of tumors. Using immunohistochemistry of tumor tissue-microarrays and sections, we confirm that the level of TACC1 protein is down-regulated in breast cancer. Finally, using the two-hybrid screen in yeast, GST pull-downs and co-immunoprecipitations, we identified two potential binding partners for TACC1, LSM7 and SmG. They constitute a conserved subfamily of Sm-like small proteins that associate with U6 snRNPs and play a role in several aspects of mRNA processing. We speculate that down-regulation of TACC1 may alter the control of mRNA homeostasis in polarized cells and participates in the oncogenic processes.
Insights
The human TACC1 gene, linked to cancer, is down-regulated in tumors, particularly breast cancer. Its reduced expression may disrupt mRNA processing and contribute to oncogenesis.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- The TACC gene family is implicated in carcinogenesis, but their precise functions remain unclear.
- Known TACC proteins have roles in translational control (Xenopus Maskin) and microtubule/centrosome association (Drosophila D-TACC).
Purpose of the Study:
- To characterize the human TACC1 gene and its protein products.
- To investigate the role of TACC1 in tumorigenesis and identify its interacting partners.
Main Methods:
- Gene expression analysis (mRNA levels) via quantitative PCR.
- Protein expression analysis using immunohistochemistry on tumor tissue microarrays.
- Yeast two-hybrid screening, GST pull-downs, and co-immunoprecipitation assays to identify binding partners.
Main Results:
- TACC1 gene expression is down-regulated in various tumor types.
- TACC1 protein levels are significantly reduced in breast cancer.
- LSM7 and SmG, components of U6 snRNPs involved in mRNA processing, were identified as TACC1 binding partners.
Conclusions:
- Down-regulation of TACC1 in tumors, especially breast cancer, suggests a tumor-suppressive role.
- TACC1 interacts with mRNA processing factors (LSM7, SmG), indicating a potential role in mRNA homeostasis.
- Altered TACC1 expression may contribute to oncogenic processes by affecting mRNA regulation.