It is well known that cigarette smoking (CS) and/or radon (Rn) induce malignant transformation in lung cells. To investigate the mechanisms underlying lung carcinogenesis induced by CS, Rn; or Rn followed by CS using BEAS-2B cell line derived from human bronchial epithelial cells. BEAS-2B cells were exposed to either Rn (20,000 Bq/m) for 30 min or CS (20%) for 10 min or Rn followed by CS for 40 min. Global and gene-specific DNA methylation modifications were measured by microarray and methylation-specific polymerase chain reaction. Cell cycle and apoptosis were determined by flow cytometry, while soft agar colony formation was conducted to assess the characteristics of malignant transformation. Data demonstrated global hypomethylation as well as gene-specific DNA methylation alterations in all treatment groups compared to unexposed control cells. In addition, Rn and CS produced DNA hypermethylation of protein tyrosine phosphatase receptor type M and ectodysplasin A2 receptor, two genes related to malignant transformation. In all treatment conditions, cell proliferation and survival of malignant cells was increased, while apoptosis was initially first passage elevated but decreased at passages 5-15. Our results indicate that aberrant DNA methylation plays an important role in Rn- and/or CS-induced malignant transformation. In addition, BEAS-2B cell line may be used as an in vitro model to investigate mechanisms underlying malignant transformation induced by ambient environmental contaminants.

Background: Suppressors of cytokine signaling family member 4 (SOCS4) was shown to serve critical and multifaceted roles in the progression of numerous cancers, including hepatocellular carcinoma, thyroid cancer, breast cancer, and lung adenocarcinoma. While, the expression and the roles of SOCS4 in esophageal squamous cell carcinoma (ESCC) remain elusive. The current study is aimed to investigate the expression pattern and functions of SOCS4 in ESCC. Methods:The relationship between SOCS4 and the clinicopathological features of ESCC was analyzed. SOCS4 expression in ESCC tissues was measured by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemical (IHC) staining. The roles of SOCS4 in modulating ESCC cell behaviors were examined using a series of assays, including cell proliferation assay, cell counting kit-8 (CCK-8) assay, cell cycle analysis, and wound-healing assay.Results: In human ESCC tissues, SOCS4 expression was up-regulated and correlated with tumor size and lymph node metastasis, however was not correlated with the overall survival (OS) of patients. SOCS4 silencing in ESCC cells resulted in the suppression of cell growth, which was related to the cell cycle. SOCS4 knockdown also inhibited nuclear factor-kappa B (NF-κB ) signaling and decreased the migratory potential of ESCC cells.Conclusions: These findings revealed that increased expression of SOCS4 in ESCC may promote the progression, proliferation, and migration by NF-κB signaling. Inhibition of SOCS4 may be a promising therapeutic strategy for ESCC.

B7 homolog 1 (B7-H1) is the most potent immunoinhibitory molecule in the B7 family. In this study, we examined the effects of tumor-associated B7-H1 on T-cell proliferation in lung cancer. The expression of B7-H1 in human adenocarcinoma A549 and mouse Lewis lung carcinoma (LLC) cells were examined by flow cytometry. To assess the in vitro effect of tumor-associated B7-H1 on T-cell proliferation, we isolated T cells from peripheral blood mononuclear cells (PBMCs) of healthy individuals, labeled them with carboxyfluorescein succinimidyl ester, and co-cultured them with A549 cells in the absence or presence of anti-B7-H1 antibody. For in vivo analysis, LLC cells were subcutaneously injected into mice treated or not with anti-B7-H1 antibody. T-cell proliferation in both in vitro and in vivo assays was analyzed by flow cytometry. In vitro, co-culturing T cells with A549 cells significantly inhibited the proliferation of the former compared with the proliferation of T cells alone (P<0.01), and the addition of B7-H1 blocking antibody dramatically reversed the inhibition of T-cell proliferation by A549 cells. Similarly, in mice bearing LLC-derived xenograft tumors, in vivo administration of anti-B7-H1 antibody significantly increased the total number of spleen and tumor T cells compared to levels in control mice that did not receive anti-B7-H1 antibody. Functionally, in vivo administration of anti-B7-H1 antibody markedly reduced tumor growth. Tumor-associated B7-H1 may facilitate immune evasion by inhibiting T-cell proliferation. Targeting of this mechanism offers a promising therapy for cancer immunotherapy.