Impact of BTG2 expression on proliferation and invasion of gastric cancer cells in vitro

Abstract

BTG2 (B cell translocation gene 2) is downregulated in several human tumors and has been known as a tumor suppressor in carcinogenesis of thymus, prostate, kidney, and liver. However, little is known about the role BTG2 plays in gastric adenocarcinoma. In the present study, we intended to investigate the influence of BTG2 on the growth, proliferation, apoptosis, invasion and cell cycle of the gastric cancer cell lines SGC7901 and MKN45. BTG2 cDNA was insected into a constitutive vector pcDNA3.1 followed by transfection in gastric cancer cell line MKN45 and SGC7901 by using liposome. Then stable transfectants were selected and appraised. The apoptosis and cell cycles of these transfectants were analyzed by using flow cytometric assay. The growth and proliferation were analyzed by cell growth curves and colony-forming assay, respectively. The invasion of these clones was analyzed by using cell migration assay. MKN-BTG2 (MKN45 with stable transfection of BTG2 gene) and SGC-BTG2 (SGC7901 with stable transfection of BTG2 gene) grew slower than their control groups, respectively. The cell counts of MKN-BTG2 in the fourth, fifth, sixth and seventh days were significantly fewer than those of control groups (P < 0.05). Those of SGC-BTG2 in the fourth fifth, sixth and seventh days were significantly fewer than those of control groups too (P < 0.05). Cell cycle analysis showed that proportions of MKN-BTG2 and SGC-BTG2 cells in G0-G1 and S were different significantly with those of their control groups, respectively (P < 0.05). The apoptosis rate of MKN-BTG2 was significantly higher than those of control groups (P < 0.05). Results of colony-forming assay showed that the colon formation rates of MKN-BTG2 and SGC-BTG2 were lower than those of their control groups (P < 0.05). The results of cell migration assay showed that the cell migration rates of MKN-BTG2 and SGC-BTG2 were not significantly different with those of their control groups (P > 0.05). BTG2 can restrain the growth and proliferation of gastric cancer cells powerfully. It can reduce some malignant phenotype of these tumor cells. But it could not impact the ability of invasion of gastric cancer cells, so could not restrain the metastasis of gastric cancer. In gastric cancer, BTG2 could be thought as a tumor-inhibiting gene in some distance, so the gene could be a potential target of gene therapy.

Cisplatin modulates B-cell translocation gene 2 to attenuate cell proliferation of prostate carcinoma cells in both p53-dependent and p53-independent pathways

“…So far, BTG2 has been demonstrated to involve in varied vital cellular functions, such as in cell cycle regulation, in which BTG2 has been found to be able to repress cell cycle progression at G1/S or G2/M phases and function as a pan cell cycle modulator in a cell- or tissue- specific manner9. Thus, BTG2 has been deemed as a tumor suppressor gene in a variety of cancers, including gastric, breast, bladder, and prostate cancer132425262728. Our results indicated that pre-apoptosis dosage of cisplatin (≤40 μM) treatments upregulated BTG2 gene expression determining by immublotting, RT-qPCR, and transient gene expression assays in both LNCaP and PC-3 cells (Figure 2a, 2b, 2c, 2e, 3c, 3d, 3e).…”

MiR-27a-3p functions as an oncogene in gastric cancer by targeting BTG2

“…As a tumor suppressor, BTG2 has been found to be down-regulated or absent in a variety of tumors, such as gastric cancer, breast cancer, and melanoma [19–21]. Moreover, dysregulation of BTG2 has been shown to contribute to gastric invasion, and metastasis [19].…”

“…As a tumor suppressor, BTG2 has been found to be down-regulated or absent in a variety of tumors, such as gastric cancer, breast cancer, and melanoma [19–21]. Moreover, dysregulation of BTG2 has been shown to contribute to gastric invasion, and metastasis [19]. Recent studies have demonstrated that BTG2 can be regulated by non-coding RNAs, including miRNAs [22–24], however its association with mature miR-27a in gastric cancer remains unknown.…”

B-cell translocation gene 2: Expression in the rat ovary and potential association with adenine nucleotide translocase 2 in mitochondria

“…Because the LH ovulatory surge induces Btg2 expression and Btg2 interacts with Ant2 in preovulatory granulosa cells, the potential role of Btg2 for promoting differentiation of ovarian granulosa cells during ovulation remains to be determined. Btg2 may have important roles in preventing carcinogenesis of the breast (Takahashi et al, 2011), stomach (Zhang et al, 2010), prostate (Ficazzola et al, 2001), kidney (Struckmann et al, 2004), and liver . It would be interesting to test whether the interaction of Btg2 with Ant2 is a common mechanism in carcinogenesis.…”