VDUP1 upregulated by TGF-β1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression

Abstract

Vitamin D 3 upregulated protein 1 (VDUP1) is a 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) upregulated protein, and it is induced by various stresses. In human tumor tissues, VDUP1 expression was downregulated. Upon stimulation by growth-inhibitory signals such as TGF-b1 and 1,25(OH) 2 D 3 , its expression was rapidly upregulated as the cell growth was retarded. The transfection of VDUP1 in tumor cells reduced cell growth. The VDUP1 expression was also increased when the cell-cycle progression was arrested. Transfection of VDUP1 induced cellcycle arrest at the G0/G1 phase, indicating that VDUP1 possesses a tumor-suppressive activity. In addition, it was found that VDUP1 interacted with promyelocytic leukemia zinc-finger, Fanconi anemia zinc-finger, and histone deacetylase 1, which are known to be transcriptional corepressors. VDUP1 itself suppressed IL-3 receptor and cyclin A2 promoter activity. Taken together, these results suggest that VDUP1 is a novel antitumor gene which forms a transcriptional repressor complex.

hnRNP G elicits tumor-suppressive activity in part by upregulating the expression of Txnip

“…However, the effect of Txnip overexpression on apoptosis is cell type-specific. For instance, the overexpression of Txnip is not sufficient to induce apoptosis in various human carcinoma cell lines [17,22], whereas the Txnip overexpression in a murine T-cell lymphoma cell line results in apoptosis [21]. We did not detect any relevant indication of apoptosis in the HEp-2 cells overexpressing Txnip (data not shown).…”

“…Txnip expression is also induced by various stresses, including H 2 O 2 , irradiation, heat shock, serum starvation, and treatment with transforming growth factor-β [16,17]. Reduced Txnip expression is found in various tumor tissues [17,18], suggesting a close association between reduced Txnip expression and tumorigenesis.…”

“…Txnip expression is also induced by various stresses, including H 2 O 2 , irradiation, heat shock, serum starvation, and treatment with transforming growth factor-β [16,17]. Reduced Txnip expression is found in various tumor tissues [17,18], suggesting a close association between reduced Txnip expression and tumorigenesis. The HcB-19 mouse strain, which has a spontaneous mutation in the Txnip gene, demonstrated an increased incidence of hepatocellular carcinoma, suggesting that Txnip is a candidate tumor suppressor gene in vivo [19].…”

The alpha subunit of Go interacts with promyelocytic leukemia zinc finger protein and modulates its functions

“…However, the molecular mechanisms by which these compounds exert their pharmacologic effects remain to be established. Several reports show that PLZF induces growth suppression, apoptosis, and cell cycle arrest [7,8,23]. Analysis of PLZF knock-out mice revealed that the protein is a growth inhibitory and proapoptotic factor in the limb bud in vivo [35].…”

“…293T and Neuro2a cells were transfected with the appropriate combinations of expression plasmids of Goα Q205L , FLAG-PLZF, IL3Rα-tk-Luc [6], and CyclinA2-Luc reporter plasmid [7], as indicated. For normalization of transfection efficiency, cells were transfected with 0.3 μg of β-gal expression plasmid (pCMV-β-gal).…”