Control of renal carcinoma TC-1 growth, cyclin/kinase and nm23 expression by IFN-gamma and TGF-beta.
To gain mechanistic insights into the growth control of renal cell carcinoma cells by IFN-gamma and TGF-beta, a recently established human renal carcinoma TC-1 cell line was treated with different concentrations of IFN-gamma and TGF-beta. Cell growth and changes in specific gene expression were evaluated. IFN-gamma exerted an antimitogenic effect on TC-1 cells, whereas TGF-beta was essentially without effect. The growth-suppressed cells had reduced expression of proliferating cell nuclear antigen (PCNA), the G2/M cell cycle transition regulatory proteins cyclin B/p34cdc2, the tumor suppressor gene pRB, and the antimetastatic gene nm23. However, levels of other cell cycle regulatory protein molecules such as cyclin D and p53 were unaffected by IFN-gamma. Thus, the antimitogenic effect of IFN-gamma may be mediated by its ability to modulate specific oncogene changes.
Hall
S
S
Department of Urology, New York Medical College, Valhalla 10595, USA.
Hsieh
T C
TC
Ng
C Y
CY
Mallouh
C
C
Wu
J M
JM
D002292:Carcinoma, Renal Cell; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D018844:Cyclin-Dependent Kinases; D004305:Dose-Response Relationship, Drug; D016195:G2 Phase; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007680:Kidney Neoplasms; D007700:Kinetics; D008938:Mitosis; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D054778:NM23 Nucleoside Diphosphate Kinases; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins; D000095043:Cyclin-Dependent Kinase-Activating Kinase