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. 2022 May;23(5):339.
doi: 10.3892/etm.2022.11269. Epub 2022 Mar 21.

BTG2 as a tumor target for the treatment of luminal A breast cancer

Runzhi Wang  1   2 , Ronghua Wang  2 , Jinjun Tian  2 , Jian Wang  3 , Huaxiao Tang  4 , Tao Wu  2 , Hui Wang  2
Affiliations

BTG2 as a tumor target for the treatment of luminal A breast cancer

Runzhi Wang et al. Exp Ther Med. 2022 May.

Abstract

As one of the most common breast cancer subtypes, luminal A breast cancer is sensitive to endocrine-based therapy and insensitive to chemotherapy. Patients with luminal A subtype of breast cancer have a relatively good prognosis compared with that of patients with other subtypes of breast cancer. However, with the increased incidence in endocrine resistance and severe side effects, simple endocrine therapy has become unsuitable for the treatment of luminal A breast cancer. Therefore, identifying novel therapeutic targets for luminal A breast cancer may accelerate the development of an effective therapeutic strategy. The bioinformatical analysis of the current study, which included KEGG and GO analyses of the GSE20437 dataset containing 24 healthy and 18 breast cancer tissue samples, identified key target genes associated with breast cancer. Moreover, survival analysis results revealed that a low expression of BTG2 was significantly associated with the low survival rate of patients with breast cancer, indicated that B-cell translocation gene 2 (BTG2) may be a potential target in breast cancer. However, BTG2 may be cancer type-dependent, as overexpression of BTG2 has been demonstrated to suppress the proliferation of pancreatic and lung cancer cells, but promote the proliferation of bladder cancer cells. Since the association between BTG2 and luminal A-subtype breast cancer remains unclear, it is important to understand the biological function of BTG2 in luminal A breast cancer. Based on the expression levels of estrogen receptor, progesterone receptor and human epidermal growth factor receptor, MCF-7 cells were selected in the present study as a luminal A breast cancer cell type. MTT, Transwell invasion and wound healing assays revealed that overexpression of BTG2 suppressed the levels of MCF-7 cell proliferation, migration and invasion. In addition, the downregulation of BTG2 at the mRNA and protein level was also confirmed in luminal A breast tumor tissue, which was consistent with the results in vitro. These results indicated that BTG2 may act as an effective target for the treatment of luminal A breast cancer.

Keywords: B-cell translocation gene 2; MCF-7 cells; bioinformatical analysis; luminal A breast cancer; target.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Volcano plot of genes in the GSE20437 dataset. Red dots indicate upregulated genes while green dots represent downregulated genes.
Figure 2
Figure 2
Top five terms revealed using the KEGG pathway analysis of differentially expressed genes in breast cancer. HTLV-1, human T-cell leukemia virus type 1; KEGG, Kyoto Encyclopedia of Genes and Genomes.
Figure 3
Figure 3
Gene Ontology terms enriched by the differentially expressed genes in breast cancer. (A) Biological process, (B) cellular component and (C) molecular function.
Figure 4
Figure 4
PPI between 236 differentially expressed genes. The PPI network was established using the Search Tool for the Retrieval of Interacting Gene/proteins (STRING; version 11.0; http://string-db.org). PPI, protein-protein interaction.
Figure 5
Figure 5
Impact of the expression of key protein-coding genes on the survival of patients with all types of breast cancer. Survival analysis of (A) BTG2, (B) DUSP1, (C) FOS, (D) FOSB, (E) IER2, (F) JUN, (G) NR4A1, (H) NR4A2 and (I) ATF3 in patients with all types of breast cancer. BTG2, B-cell translocation gene 2; DUSP1, dual specificity phosphatase 1; FOS, proto-oncogene c-FOS; FOSB, protein FOSB; JUN, proto-oncogene c-Jun; NR4A, nuclear receptor subfamily 4 group A member; ATF3, activating transcription factor 3.
Figure 6
Figure 6
Difference in BTG2 expression between luminal A breast cancer tissues and healthy tissues. BTG2, B-cell translocation gene 2; 0, no value (n=4); 1, invasive breast carcinoma (n=154).
Figure 7
Figure 7
Impact of BTG2 expression level, cancer type, menopause status and race on the survival of patients with breast cancer and mutations in BRCA. Impact of (A) BTG2 expression level, (B) cancer type, (C) menopause status and (D) race on the survival of patients with breast cancer and mutations in BRCA. BTG2, B-cell translocation gene 2; BRCA, breast cancer type 1 susceptibility protein; HER2, human epidermal growth factor receptor; -ve, negative; +ve, positive.
Figure 8
Figure 8
Detection of BTG2 expression levels following transfection in MCF-7 cells. (A and B) BTG2 protein expression levels were determined in NC, OE-NC and OE-BTG2 groups of MCF-7 cells using western blot analysis. (C) BTG2 mRNA expression levels were determined in NC, OE-NC and OE-BTG2 groups of MCF-7 cells. Data represent three independent experimental repeats. ***P<0.001. BTG2, B-cell translocation gene 2; NC, negative control; OE, overexpression.
Figure 9
Figure 9
Proliferation of NC, OE-NC and OE-BTG2 groups of MCF-7 cells. **P<0.01 and ***P<0.001 vs. the NC group. BTG2, B-cell translocation gene 2; NC, negative control; OE, overexpression; OD, optical density.
Figure 10
Figure 10
BTG2 suppressed the invasion and migration of MCF-cells. Role of BTG2 in the (A and B) invasion and (C and D) migration of NC, OE-NC and OE-BTG2 groups of MCF-7 cells (magnification, x100). Data represent three independent experimental repeats. Dashed lines indicate the width of the wound. ***P<0.001. BTG2, B-cell translocation gene 2; NC, negative control; OE, overexpression.
Figure 11
Figure 11
BTG2 expression in luminal A breast cancer and paracarcinoma tissues of patients. Relative (A) mRNA and (B) protein expression of BTG2 in luminal A breast cancer and paracarcinoma tissues. B1-B4, luminal A breast cancer tissues; X1-X4, paracarcinoma tissues. (C) Relative mRNA expression levels of BTG2 in luminal A breast cancer and paracarcinoma tissues. ***P<0.001. BTG2, B-cell translocation gene 2.
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