Tissue Inhibitor of Metalloproteinase-4 Triggers Apoptosis in Cervical Cancer Cells.
Tissue inhibitor of metalloproteinase-4 (TIMP-4) is a member of extracellular matrix (ECM) metalloproteinases inhibitors that has pleiotropic functions. However, TIMP-4 roles in carcinogenesis are not well understood. Cell viability and flow cytometer assays were employed to evaluate cell death differences between H-Vector and H-TIMP-4 cell lines. Immunobloting and semi-quantitative RT-PCR were used to evaluate the expression of apoptosis regulators. We showed that TIMP-4 has apoptosis-sensitizing effects towards several death stimuli. Consistent with these findings, regulators of apoptosis from Inhibitors of Apoptosis Proteins (IAP), FLICE-like inhibitor proteins (FLIP) and Bcl-2 family members were modulated by TIMP-4. In addition, TIMP-4 knockdown resulted in cell survival increase after serum deprivation, as assessed by clonogenic cell analyses. This report shows that TIMP-4 regulates carcinogenesis through apoptosis activation in cervical cancer cells. Understanding TIMP-4 effects in tumorigenesis may provide clues for future therapies.
Basic Research Subdivision, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan. Mexico, D.F. C.P.14610, Mexico.
Floria
F
Lizarraga
Basic Research Subdivision, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan. Mexico, D.F. C.P.14610, Mexico.
Gisela
G
Ceballos-Cancino
Basic Research Subdivision, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan. Mexico, D.F. C.P.14610, Mexico.
Magali
M
Espinosa
Basic Research Subdivision, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan. Mexico, D.F. C.P.14610, Mexico.
Karla
K
Vazquez-Santillan
Basic Research Subdivision, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan. Mexico, D.F. C.P.14610, Mexico.
Vilma
V
Maldonado
Basic Research Subdivision, National Institute of Genomic Medicine, Functional Genomics Laboratory, Periferico Sur 4809, Col. Arenal Tepepan, Del. Tlalpan. Mexico, D.F. C.P.14610, Mexico.
Jorge
J
Melendez-Zajgla
D017209:Apoptosis / Q000502:physiology*; D063646:Carcinogenesis / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D019714:Tissue Inhibitor of Metalloproteinases / Q000502:physiology*; D002583:Uterine Cervical Neoplasms / Q000503:physiopathology*; D000097792:Tissue Inhibitor of Metalloproteinase-4
D020169:Caspases; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4