Knockdown of IG20 gene expression renders thyroid cancer cells susceptible to apoptosis.
OBJECTIVE
The aim of the study was to investigate the expression and function of the IG20 gene in thyroid cancer cell survival, proliferation, and apoptosis.


METHODS
We determined the expression levels of the major isoforms of IG20 by quantitative RT-PCR in normal and thyroid tumor tissues/cell lines. We evaluated the functional consequence of IG20 knockdown in WRO (follicular carcinoma) and FRO (anaplastic carcinoma) thyroid cancer cell lines by measuring spontaneous, TNFalpha-related apoptosis-inducing ligand (TRAIL), and TNFalpha-induced apoptosis.


RESULTS
The IG20 gene expression levels were higher in benign and malignant thyroid tumors and in WRO and FRO cells relative to normal tissues. Predominantly, MADD and DENN-SV isoforms of IG20 gene were expressed. IG20 knockdown resulted in increased spontaneous, TRAIL-, and TNFalpha-induced apoptosis in WRO, but not FRO, cells. FRO cell resistance to apoptosis is likely due to caspase-8 deficiency.


CONCLUSIONS
IG20 knockdown renders WRO cells more susceptible to spontaneous, TRAIL-, and TNFalpha-induced apoptosis and thus demonstrates the prosurvival function of the IG20 gene in thyroid cancer. These observations, combined with overexpression of IG20 noted in thyroid tumor tissues, may suggest a potential role in thyroid cancer survival and growth and indicate that IG20 may be targeted either alone or in conjunction with TRAIL or TNFalpha treatment in certain thyroid cancers.
Subramanian
Mahesh
M
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Pilli
Tania
T
Bhattacharya
Palash
P
Pacini
Furio
F
Nikiforov
Yuri E
YE
Kanteti
Prasad V
PV
Prabhakar
Bellur S
BS
D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000473:pathology; D017398:Alternative Splicing; D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000235:genetics*; D014644:Genetic Variation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D055029:Inverted Repeat Sequences / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers; D004273:DNA, Neoplasm; D053418:Death Domain Receptor Signaling Adaptor Proteins; D020662:Guanine Nucleotide Exchange Factors; C105852:MADD protein, human; D012334:RNA, Neoplasm