Studies On The Expression Of Endoplasmic Reticulum Molecular Chaperone GRP94, GRP78 And PDI In Human Lung Cancer Tissues

Approximately one-third of newly synthesized proteins are transported to the lumen of the endoplasraic reticulum(ER) for posttranslational modifications of the proteins such as folding and oligomerization. Alterations in horaeostasis after various cellular stresses, which prevent protein folding and cause accumulation of misfolding proteins in the ER, have the potential to induce cellular damage. Normal cells respond to ER stress by increasing transcription of genes encoding ER-resident molecular chaperones such as GRP94, GRP78 and PDI to facilitate protein folding. Lung cancers harbor stressful microenvironments of hypoxia, acidosis, and glucose deprivation due to inadequate or inefficient vasculature. Such pathological conditions can induce the expression of molecular chaperones such as GRP94, GRP78/Bip and PDI.The thesis analyzed the expressions of GRP94, GRP78 and PDI at the level of mRNA and protein with the methods of RT-PCR, immunohistalchemistry and/or Western blot in a series of 54 consecutive patients with lung cancer who underwent surgical resections in order to better understand the three chaperones ' role in human lung cancer. It mainly focuses on: 1. Compare the expressions of GRP94, GRP78 and PDI between the lung cancer and normal lung tissues. 2. Within the lung cancer and normal lung tissues, compare the relationship between the expressions of GRP94, GRP78 and PDI to various differentiation, clinical stage and pathologic type of the tumors respectively. Among all the patients, only 24 were assayed by the method of Western blot at the same time.The mainly results are as follows:First, RT-PCR showed: GRP94 and GRP78 were expressed both in lung cancer and normal lung tissues, whereas the positive rates of PDI of them were 88.9% and 75.9% respectively. But there were obviously overexpressions of the three chaperones in the cancer tissues as compared to the normal tissues. Among the three chaperones, the GRP94' s overexpression was the most.Within the lung cancer tissues, there were stronger expressions of the three chaperones in the poorly differentiated tumors than that of mild-highAbstractdifferentiated tumors, and the differences of GRP94 and GRP78 were significant, but PDI was no significant. And there were also stronger expressions of the three chaperones in the III stage than that of the I and II stage tumors, but only the GRP94' s difference was significant, the other two were not. No statistically significant differences of the three chaperones were found among the various pathologic types of the tumors.Within the normal lung tissues, there were stronger expressions of the three chaperones in the poorly differentiated tumors than that of mild-high differentiated tumors, and the differences of the chaperones were all significant. But no statistically significant differences were found among the various pathologic types and clinical stage of the tumors.Secondly, Western blot analysis showed that it was easy to detect the three chaperones in both the lung cancer and the normal lung tissues of the 24 patients. But there were obviously overexpressions of them in the lung cancer tissues. The differences of the three chaperones between the two groups were all significant. And there were nearly a 2 fold increase of GRP94 and GRP78 protein in lung cancer tissues compare to normal lung tissues.Within the lung cancer tissues, there were stronger expressions of the three chaperones in the poorly differentiated tumors than that of mild-high differentiated tumors, and the difference of them were all significant. There were significantly stronger expressions of GRP94 and GRP78 in the III stage than that of the I and II stage tumors, but no difference was found of PDI among different stage of the tumors. No statistically significant differences were found among the various pathologic types of the tumors of the three chaperones.Within the normal lung tissues, there were significantly stronger expressions of the three chaperones in the poorly differentiated tumors than that of...