title: Promotive effects of cell proliferation and chromosomal instability induced by tribbles-related protein 3 in mouse mammary tumor cells.
abstract: Tribbles-related protein 3 (TRB3) has been shown to be a crucial modulator of tumorigenesis. However, the precise role and the functional morphology of TRB3 are not clearly understood. To elucidate these enigmas we established the cell line, M2TRB3, by introducing the human TRB3 gene and protein in Cl66M2 (M2) mouse mammary tumor cells. This cell line stably expressed the TRB3 gene and protein. After 72 h of cell culture, there was a 34% increase in the growth of M2TRB3 cells compared to the control M2 mock cells. The mean volume of the tumors originating from the M2TRB3 cells was significantly increased by 38% when compared to the mean volume of the M2 mock tumors, and the proliferating cell nuclear antigen (PCNA) labeling index in the M2TRB3 tumors was higher when compared to that of the M2 and M2 mock cells. In the tumor tissue samples, the mean diameter of nuclei in the M2TRB3 tumor cells (9.4±0.3 µm) showed a significant increase compared to that of the M2 mock tumor cells (7.0±0.2 µm). M2TRB3 cells also showed a marked increase in the population of tetraploid or octaploid nuclei compared to M2 mock cells bearing mainly either diploid or tetraploid nuclei. Western blot analysis revealed the overexpression of cyclin B1 and cyclin D1 in M2TRB3 cells when compared to that in the M2 mock cells. These novel findings provide further evidence that TRB3 promotes cell proliferation and chromosomal instability by causing polyploidization during development.
authors: Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences and Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors: Yuto
authors: Y
authors: Sakai
authors: Katsumi
authors: K
authors: Fukamachi
authors: Mitsuru
authors: M
authors: Futakuchi
authors: Hidetoshi
authors: H
authors: Hayashi
authors: Masumi
authors: M
authors: Suzui
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000096:biosynthesis; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D043171:Chromosomal Instability / Q000235:genetics*; D056744:Cyclin B1 / Q000096:biosynthesis; D019938:Cyclin D1 / Q000096:biosynthesis; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis; D051358:Cyclin-Dependent Kinase 4 / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D018797:Cell Cycle Proteins; D056744:Cyclin B1; D012333:RNA, Messenger; C474830:TRB3 protein, mouse; D019938:Cyclin D1; D016203:CDC2 Protein Kinase; C495893:Cdk2 protein, mouse; C495902:Cdk4 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4