Human secreted frizzled-related protein is down-regulated and induces apoptosis in human cervical cancer.
To identify genes involved in cervical carcinogenesis, the mRNA differential display method was used. A 220-bp cDNA fragment called CA11 was present in normal cervical tissue but not in primary cervical cancer tissue or cervical cancer cell lines. CA11 exhibited 98% homology with the recorded human secreted frizzled-related protein (hsFRP) sequence. A dominant hsFRP mRNA transcript of approximately 4.6 kb was present in three normal cervical tissues examined. Expression of the transcript was nearly absent from three cervical cancer tissues and from five human cervical cancer-derived cell lines. Results from in situ hybridization showed that the hsFRP transcript was confined to the normal cervical epithelial layer. When hsFRP-transfected HeLa and CUMC-6 cervical cancer cells were cultured in serum-free medium, most of the cells died within 8 days. This effect is associated with the apoptotic process. The caspase-3 inhibitor 1, Ac-DEVD-CHO, blocked hsFRP-induced apoptotic cell death. Additionally, cleavage of poly (ADP-ribose) polymerase in hsFRP-transfected cells was confirmed by colorimetric assay. These results indicate that the hsFRP gene probably functions as a tumor suppressor in normal cervical epithelium and down-regulation of hsFRP contributes to development of cervical cancer.
Ko
Jesang
J
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, 138-736, Korea.
Ryu
Ki Sung
KS
Lee
Young Han
YH
Na
Doe Sun
DS
Kim
Yoon Suk
YS
Oh
Young Mi
YM
Kim
In Sik
IS
Kim
Jin Woo
JW
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D002584:Cervix Uteri / Q000166:cytology / Q000473:pathology; D016895:Culture Media, Serum-Free; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D009842:Oligopeptides / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D000099274:Frizzled-Related Proteins
D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases; D016895:Culture Media, Serum-Free; D015853:Cysteine Proteinase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009842:Oligopeptides; D011506:Proteins; D000099274:Frizzled-Related Proteins; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; C505407:CASP3 protein, human