ABSTRACT
Human epidermal growth factor receptor 2-positive (HER2+) breast cancer, which accounts for 15-20% of all breast cancer, is associated with tumor recurrence and poor prognosis. RAS association domain family protein 1 subtype A (RASSF1A) is a tumor suppressor that is silenced in a variety of human cancers. The present study aimed to investigate the role of RASSF1A in HER2+ breast cancer and the therapeutic potential of RASSF1A-based targeted gene therapy for this malignancy. RASSF1A expression in human HER2+ breast cancer tissues and cell lines was evaluated by reverse transcription PCR and western blot analysis. The associations between tumorous RASSF1A level and tumor grade, TNM stage, tumor size, lymph node metastasis and five-year survival were examined. HER2+ and HER2-negative (HER2-) breast cancer cells were transfected with a lentiviral vector (LV-5HH-RASSF1A) that could express RASSF1A under the control of five copies of the hypoxia-responsive element (5HRE) and one copy of the HER2 promoter (HER2p). Cell proliferation was evaluated by the MTT and colony formation assays. It was found that tumorous RASSF1A level was negatively associated with tumor grade (P=0.014), TNM stage (P=0.0056), tumor size (P=0.014) and lymph node metastasis (P=0.029) and positively associated with five-year survival (P=0.038) in HER2+ breast cancer patients. Lentiviral transfection of HER2+ breast cancer cells resulted in increased RASSF1A expression and decreased cell proliferation, especially under hypoxic conditions. However, lentiviral transfection of HER2-breast cancer cells did not affect RASSF1A expression. In conclusion, these findings verified the clinical significance of RASSF1A as a tumor suppressor in HER2+ breast cancer and supported LV-5HH-RASSF1A as a potential targeted gene therapy for this malignancy.
ABSTRACT
Reticulocalbin (RCN) family members could play oncogenic roles in human malignancies and facilitate tumor cell proliferation and metastasis. However, the expression pattern and potential function of Reticulocalbin 2 (RCN2) in colorectal cancer has not been addressed yet. In the present study, we investigated the protein expression of RCN2 by immunohistochemistry assay, and analyzed its association with tumor progression, recurrence and prognosis in 326 cases of patients. Results suggested that the expression of RCN2 was up-regulated in colorectal cancer compared with paired adjacent nontumor specimens. RCN2 expression was closely related to tumor size and the depth of invasion. Kaplan-Meier analysis proved that RCN2 was associated with both disease-free survival and overall survival of patients with colorectal cancer. Moreover, cox's proportional hazards analysis showed that high RCN2 expression was an independent prognostic marker of poor outcome. Consistently, overexpressing RCN2 promoted CRC cell proliferation both in vitro and in vivo and knockdown RCN2 showed the opposite results. These results provided the first evidence that RCN2 level was increased in colorectal cancer and significantly correlated with tumor growth and proliferation. It also indicated that RCN2 might serve as a potential marker of tumor recurrence and prognosis of colorectal cancer.
ABSTRACT
BACKGROUND: POLG is a gene that codes for the catalytic subunit of the mitochondrial DNA polymerase, which is involved in the replication of mitochondrial DNA. Genetic variants in mitochondrial DNA polymerase-γ (POLG) have been associated with several malignancies. However, as an important metabolic tissue, association between genetic polymorphisms of POLG and the prognosis and mitochondrial DNA (mtDNA) content in hepatocellular carcinoma (HCC) remains unknown. Here we investigated the association between in POLG with the prognosis and mitochondrial DNA (mtDNA) content in hepatocellular carcinoma (HCC). METHODS: Three nucleotide polymorphisms (SNPs) of rs1061316, rs2247233 and rs758130 in POLG were examined in 416 patients from two cohorts undergoing transcatheter arterial chemoembolization treatment. Leukocyte mtDNA content from 216 patients in cohort 2 was measured using a real-time PCR-based method. The association of SNPs with prognosis and of mtDNA content of patients was analyzed. RESULTS: The rs758130 in POLG gene was significantly associated with the prognosis of patients in a dose-dependent manner. Moreover, GG genotype in rs1061316 showed significantly high mtDNA content, an indicator of better prognosis. CONCLUSIONS: Our study for the first time demonstrates that rs1061316 and rs758130 in POLG is associated with the prognosis and leukocyte mtDNA content in HCC patients.
