CASC2a gene is down-regulated in endometrial cancer.
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.


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.


CONCLUSIONS
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.
Baldinu
Paola
P
Istituto Chimica Biomolecolare-C.N.R., 07040 Li Punti-Sassari, Italy.
Cossu
Antonio
A
Manca
Antonella
A
Satta
Maria P
MP
Sini
Maria C
MC
Palomba
Grazia
G
Dessole
Salvatore
S
Cherchi
Pierluigi
P
Mara
Laura
L
Tanda
Francesco
F
Palmieri
Giuseppe
G
D001483:Base Sequence; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*
D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C484713:long non-coding RNA CASC2, human