Transforming growth factor-beta 1 induces apoptosis through down-regulation of c-myc gene and overexpression of p27Kip1 protein in cervical carcinoma.
Transforming growth factor-beta 1 (TGF-beta 1) is known to be a potent growth inhibitor for many cell types, including most epithelial cells. In skin keratinocytes, TGF-beta 1 has been shown to inhibit growth and to rapidly reduce c-myc expression. However, the molecular mechanism of TGF-beta 1 action on cell growth of cervical carcinoma has not yet been elucidated. We thus assessed the effect of TGF-beta 1 on the growth of cervical carcinoma cell lines. Two cervical squamous carcinoma cell lines, CUMC-3 and CUMC-6, were incubated with varying concentrations of TGF-beta 1, and growth inhibition was evaluated with tetrazolium-based colorimetric assay. After culture in TGF-beta 1 for 24 h, inhibition of growth was detected in a dose-dependent manner at concentrations of 0.1-10 ng/ml in both cell lines. This effect of TGF-beta 1 on cultured carcinoma cells was associated with apoptotic process including oligonucleosomal ladder DNA and apoptotic body formations. Northern blot analysis revealed c-myc mRNA expression was suppressed by 10 ng/ml of TGF-beta 1 following 3 h of treatment in both cell lines. Western blot analysis showed that the level of p27Kip1 protein was increased after TGF-beta 1 treatment in both cell lines. These results suggest that the mechanisms by which TGF-beta 1 inhibits the growth of cervical carcinoma are complex and may include effects on down-regulation of c-myc gene, and overexpression of p27Kip1 protein.
Kim
J W
JW
Department of Obstetrics and Gynecology, Kangnam St. Mary's Hospital, Seoul, Korea.
Kim
H S
HS
Kim
I K
IK
Kim
M R
MR
Cho
E Y
EY
Kim
H K
HK
Lee
J M
JM
Namkoong
S E
SE
D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27