Candidate tumor suppressor, HCCS-1, is downregulated in human cancers and induces apoptosis in cervical cancer.
To identify the genes involved in cervical carcinogenesis, we applied the mRNA differential display method and identified a candidate tumor suppressor gene, HCCS-1, which was present in normal cervical tissue but absent in cervical cancer, metastatic lymph node and CUMC-6 cervical cancer cell line. HCCS-1 transcripts were expressed in many normal tissues including leukocyte, lung, spleen, liver, heart and uterine cervix. Its expression was absent in 8 human cancer cell lines. HCCS-1-transfected HeLa cells exhibited growth inhibition by about 50%. This inhibitory effect of HCCS-1 on cervical cancer cells was associated with apoptotic process including DNA fragmentation. HCCS-1-transfected HeLa cells were shown to release cytochrome c from mitochondria, which activates caspase-9 and -3 and finally results in cleavage of poly(ADP-ribose) polymerase. Apoptosis formation was detected by propidium-iodide/annexin V. HCCS-1-transfected HeLa cells were more sensitive to adriamycin or UVC ray triggered apoptosis. These results suggest that HCCS-1 is downregulated in multiple human tumor types and may serve as a candidate tumor suppressor gene through apoptotic pathway against human cervical cancer.
Kim
Tae E
TE
Molecular Genetic Laboratory, Catholic Research Institutes of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Kim
Yong W
YW
Hwang
Seung Y
SY
Shin
Seung M
SM
Shin
Jin W
JW
Lee
Young H
YH
Shin
Sun Y
SY
Han
Ku T
KT
Lee
Joon M
JM
Namkoong
Sung E
SE
Kim
Jin W
JW
D000595:Amino Acid Sequence; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D003574:Cytochrome c Group / Q000378:metabolism; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006367:HeLa Cells / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D006801:Humans; D008207:Lymphatic Metastasis; D008969:Molecular Sequence Data; D011506:Proteins / Q000502:physiology*; D014162:Transfection; D025521:Tumor Suppressor Proteins; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D033921:Vesicular Transport Proteins
D017304:Annexin A5; D003574:Cytochrome c Group; D011506:Proteins; D025521:Tumor Suppressor Proteins; C503307:VPS53 protein, human; D033921:Vesicular Transport Proteins; D004317:Doxorubicin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases