Candidate tumor suppressor, HCCS-1, is downregulated in human cancers and induces apoptosis in cervical cancer.

Abstract

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.