APRIL, BCMA and TACI proteins are abnormally expressed in non-small cell lung cancer

Abstract

Lung cancer is the leading cause of cancer-associated mortality. Non-small cell lung cancer (NSCLC) accounts for >80% of lung cancers. The overall survival for NSCLC is dismal, with a 5-year survival of <5% for patients. Thus, identifying an effective biomarker for early diagnosis of lung cancer is the first essential step to reduce mortality. It has been recognized that certain inflammatory and immune responses are important in lung cancer development and prevention. The present study demonstrated that, in NSCLC, a proliferation-inducing ligand (APRIL), B-cell maturation antigen (BCMA)and transmembrane activator and CAML interactor (TACI) proteins are abnormally expressed by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blotting. In addition, the expression of APRIL, BCMA and TACI were observed to be involved in extracellular signal-regulated kinase (ERK)1/2 activation in A549 cells. Overall, the present study provides evidence that APRIL and its receptors, BCMA and TACI, may play roles in the biological processes of NSCLC tumors through the ERK1/2 signaling pathway.

Keywords: APRIL; BCMA; ERK1/2; TACI; lung cancer.

Figure 1.

APRIL expression is increased in NSCLC samples. (A-C) Immunohistochemistry study of APRIL expression in paraffin-embedded NSCLC samples. Representative images of APRIL staining (brown) in (A) adenocarcinoma and (B and C) squamous cell carcinoma. (D) Representative images of negative staining (without primary antibody) of the sample in panel C. Magnification, ×100. APRIL, a proliferation-inducing ligand; NSCLC, non-small cell lung cancer.

Figure 2.

BCMA and TACI expression is increased in NSCLC samples. Immunohistochemistry study of BCMA and TACI expression in paraffin-embedded NSCLC samples. (A) Representative images of BCMA staining (brown). (B) Representative images of TACI staining (brown) in lung cancer. Magnification, ×100. BCMA, B-cell maturation antigen; TACI, transmembrane activator and CAML interactor; NSCLC, non-small cell lung cancer.

Figure 3.

APRIL, BCMA and TACI expression profile in NSCLC tissue samples, as analyzed by WB and RT-qPCR. (A) mRNA expression of APRIL, BCMA and TACI in NSCLC samples, as measured by RT-qPCR, relative to that of β-actin. (B) Protein expression of BCMA and TACI in NSCLC samples, as measured by WB, relative to that of β-actin. APRIL, a proliferation-inducing ligand; BCMA, B-cell maturation antigen; TACI, transmembrane activator and CAML interactor; NSCLC, non-small cell lung cancer; N, normal; T, tumor; C, cancer; mRNA, messenger RNA; RT-qPCR, reverse transcription-quantitative polymerase chain reaction; WB, western blotting.

Figure 4.

APRIL activates the mitogen-activated protein kinase ERK1/2 in A549 cells. (A) Extracts from A549 cells transfected with BCMA siRNA and TACI siRNA were subjected to western blotting and probed with antibodies against pERK1/2 and total ERK1/2. (B) Bar graphs represent the mean ± SEM (n=5; *P<0.05, one-way ANOVA). si, small interfering; NC, negative control; N.S., not significant; APRIL, a proliferation-inducing ligand; BCMA, B-cell maturation antigen; TACI, transmembrane activator and CAML interactor; ERK, extracellular signal regulated kinase; p, phosphorylated; WB, western blotting; ANOVA, analysis of variance; SEM, standard error of the mean.si, small interfering; NC, negative control; N.S., not significant; APRIL, a proliferation-inducing ligand; BCMA, B-cell maturation antigen; TACI, transmembrane activator and CAML interactor; ERK, extracellular signal-regulated kinase; p, phosphorylated; WB, western blotting; ANOVA, analysis of variance; SEM, standard error of the mean.