Overexpression of endoplasmic reticulum molecular chaperone GRP94 and GRP78 in human lung cancer tissues and its significance

Abstract

Background: To investigate the relationship between the expression of glucose-regulated protein94 (GRP94) and GRP78 at the level of mRNA and protein in vivo and in human lung cancer. Methods: RT-PCR, real-time PCR, immunohistochemistry and/or Western blot were used in 54 cases of lung cancer and corresponding normal lung tissue. Results: The expression pattern of GRP94 and GRP78 was similar. There was a significant overexpression of GRP94 and GRP78 at both mRNA and protein levels in cancer tissues as compared to normal tissues. The relative levels of GRP94 and GRP78 mRNA evaluated by RT-PCR in cancer and normal lung tissue were: GRP94: 3.48 ± 2.06 versus 2.01 ± 1.83; GRP78: 3.64 ± 1.87 versus 2.21 ± 1.54; by real-time PCR were: GRP94: 2.89 ± 0.64 versus 1.12 ± 0.54; GRP78: 2.56 ± 0.82 versus 0.96 ± 0.42. The relative level of GRP94 and GRP78 protein by Western blot in cancer and normal lung tissue were: GRP94: 3.46 ± 1.72 versus 1.81 ± 0.92; GRP78: 4.84 ± 2.55 versus 1.91 ± 1.15, indicating an approximate 2-fold and a 3-fold increase in GRP94 and GRP78 protein in cancer tissue as compared with normal tissue. Immunohistochemistry result for GRP94 and GRP78 in cancer and normal tissue was similar, that is: a stronger stain was observed in cancer tissue (main intensity of staining ++ to +++) compared to normal tissue (main intensity of staining + to ++). All the difference for GRP94 and GRP78 between the two tissues were significant ( p < 0.05). Furthermore, the overexpression of GRP94 and GRP78 in the cancer tissue correlated with grade of differentiation and stage of tumors. There was stronger expression in poorly differentiated tumors than in well-moderately differentiated tumors ( p < 0.05). There was also stronger expression in stage III than in stages I and II tumors ( p < 0.05). No statistically significant differences were found among various pathologic types of tumors. Correlation analysis showed that there is a positive correlation between GRP94 and GRP78. Conclusion: The expression pattern of GRP94 and GRP78 was similar in human lung cancer. They both were related with the differentiation and progression of the cancer. The expression at mRNA and protein level may be valuable in evaluating the grade of differentiation and clinical stage of human lung cancer.