Background: Chromosome 10q25-q26 has been strongly correlated to endometrial tumorigenesis. A novel human gene, CASC2, has previously been identified at chromosome 10q26. One out of the three alternative transcripted forms, CASC2a, has been demonstrated to be mutated at a low frequency in endometrial cancer (EC). In this study, the role of the CASC2a gene in cancer has been further defined. Materials and Methods: Tumour and corresponding normal tissues were analysed for CASC2a mRNA expression by real-time RT-PCR and mutation status by PCR-based approaches. Results: A significantly decreased level of CASC2a transcripts was observed in 13/17 (76%) EC tissues, as well as in 6/9 (67%) colorectal cancers. Exogenous expression of CASC2a in undifferentiated AN3CA endometrial cancer cells inhibited cellular growth in anchorage-independent growth assays. Finally, infrequent CASC2a mutations were able to impair the gene function. Conclusion: Altogether, our findings strongly suggest that CASC2a may act as a tumour suppressor gene, with both epigenetic and genetic alterations concurring to gene inactivation. Down-regulation of CASC2a may provide a growth advantage in EC cells.
CASC2a gene is downregulated in endometrial cancer.
Manca A;Sini MC;Palomba G;Palmieri G
2007
Abstract
Background: Chromosome 10q25-q26 has been strongly correlated to endometrial tumorigenesis. A novel human gene, CASC2, has previously been identified at chromosome 10q26. One out of the three alternative transcripted forms, CASC2a, has been demonstrated to be mutated at a low frequency in endometrial cancer (EC). In this study, the role of the CASC2a gene in cancer has been further defined. Materials and Methods: Tumour and corresponding normal tissues were analysed for CASC2a mRNA expression by real-time RT-PCR and mutation status by PCR-based approaches. Results: A significantly decreased level of CASC2a transcripts was observed in 13/17 (76%) EC tissues, as well as in 6/9 (67%) colorectal cancers. Exogenous expression of CASC2a in undifferentiated AN3CA endometrial cancer cells inhibited cellular growth in anchorage-independent growth assays. Finally, infrequent CASC2a mutations were able to impair the gene function. Conclusion: Altogether, our findings strongly suggest that CASC2a may act as a tumour suppressor gene, with both epigenetic and genetic alterations concurring to gene inactivation. Down-regulation of CASC2a may provide a growth advantage in EC cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
