High expression of survivin and its splice variants survivin ΔEx3 and survivin 2 B in oral cancers.
OBJECTIVE
We have previously reported inactivation of p53 in 46% of Indian patients with oral cancer. Survivin, a p53 target gene and an inhibitor of apoptosis protein (IAP), is overexpressed in several cancers, including oral cancers. Studies assessing the role of survivin and its splice variants in oral cancers are, however, rare.


METHODS
The expression of 6 survivin isoforms in 4 oral cancer cell lines (AW8507, AW13516, UPCI-SCC040, UPCI-SCC029 B), a dysplastic oral cell line (DOK), 75 paired oral tumor and adjacent normal tissues, and 12 normal oral tissue samples from healthy individuals was analyzed by real-time PCR. The expression was correlated with clinicopathologic parameters, which included age, sex, tumor-node-metastasis (TNM) staging, tobacco and/or alcohol consumption, site, and differentiation status of tumor.


RESULTS
This is the first study to find overexpression of the 6 characterized survivin isoforms in oral cancers compared with normal tissues (P < .05). Additionally, a significant (P < .05) correlation among the fold changes of all 6 survivin isoforms was observed. Survivin wild type (wt) was the predominantly expressed isoform in oral cell lines and tumor tissues versus normal tissues (P < .05). Among the minor isoforms, survivin ΔEx3 and survivin 2 B were dominantly expressed, whereas survivin 2 α and survivin 3 α overexpression was found for the first time. Further high survivin 3 B expression exhibited a significant association (P < .05) with poorly differentiated tumors. Interestingly the combined expression of the antiapoptotic survivin isoforms, survivin wt, survivin ΔEx3, and survivin 3 B, exhibited a significant association with TNM staging of the tumor.


CONCLUSIONS
Our studies thus indicate that oral cancers overexpress the antiapoptotic survivin variants, which exhibit an association with advanced tumor stage, implying a role for these variants in oral tumorigenesis.
Teni Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, India.
Rupa
R
Mishra
Genomics Applications and Information Technology (GANIT) Labs, Institute of Bioinformatics and Applied Biotechnology (IBAB), Bangalore, India.
Vinayak
V
Palve
Epidemiology and Clinical Trial Unit (ECTU), Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, India.
Sadhana
S
Kannan
Teni Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, India.
Sagar
S
Pawar
Teni Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, India. Electronic address: Tteni@actrec.gov.in.
Tanuja
T
Teni
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007194:India; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D020033:Protein Isoforms; D060888:Real-Time Polymerase Chain Reaction; D000077022:Survivin; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D000077022:Survivin