Induction of glucose regulated proteins during growth of a murine tumor

Abstract

Chronic anoxia, glucose starvation, low pH, and numerous other conditions induce the glucose-regulated system of stress proteins (GRPs), whose principal members are observed at 78, 94, and 170 kDa. These stresses may be expected to occur during growth in untreated tumors. To examine the possibility that GRPs are correspondingly induced, we have examined the protein profiles of small (< 0.1 g), intermediate (0.2-0.8 g), and large (> 1.8 g) radiation-induced fibrosarcoma (RIF) tumors grown on C3H mice. One and two-dimensional gel electrophoresis indicate that the principal GRPs at 78 and 94 are coordinately and substantially increased in large tumor masses, relative to the small, and may be partially increased in the intermediate tumors. Necrotic material removed from large tumors exhibited an identical pattern of GRP induction with no visible indication of protein degradation and also contained a significant fraction of viable cells. Western blot analysis using rabbit antisera raised against the 78 and 170 kDa GRPs also demonstrated the enhanced accumulation of these proteins in the large tumors. The antibody against the 170 kDa GRP was also capable of detecting the induction of this stress protein in large tumors by indirect immunofluorescence analysis. Northern blot studies using a probe for the GRP 78 gene also showed an increase in GRP 78 message in large tumors as well as in RIF cells exposed to anoxic stress in vitro. Two-dimensional gel electrophoresis indicated that the major heat shock proteins at 70 and 90 kDa were not increased in the larger tumors, and the amount of the 90 kDa species was reduced. Finally, the quantity of vimentin and its degradation products is significantly diminished in large tumors and in anoxic cells. This study demonstrates that RIF tumor cells undergo a glucose regulated stress response in situ during tumor growth.

The expression of glucose regulated protein-94 in colorectal carcinoma cells treated by sodium butyrate

“…Furthermore, GRP94 has also been identified as a murine tumor rejection antigen, indicating that to some extent it can also reside on the cell surface [20]. It has been shown that large amount of GRPs proteins were synthesized during tumor growth, HSP90 protein, in this case, was repressed [13]. The possible explanation might be that GRPs proteins is likely to be triggered by abnormalities in protein processing or folding in the endoplasmic reticulum, which, in some cases, has been shown to be resulted from abnormal glycosylation.…”

“…GRPs was also induced by various stresses to function as molecular chaperones [11], [12]. Enhanced expression of GRPs during the growth of cancer cells imply its close relationship with the cell growth [13]. However, few reports have studied the expression of Grps genes especially during the course of tumor growth and differentiation in comparison with those of HSPs.…”

Chaperoning Function of Stress Protein grp170, a Member of the hsp70 Superfamily, Is Responsible for its Immunoadjuvant Activity

“…Grp170 is a major stress protein/molecular chaperone resident in the endoplasmic reticulum (ER; refs. [14][15][16][17] that is induced by stress conditions such as hypoxia, ischemia, and interference in calcium homeostasis (18). Studies have shown that grp170 is associated with the folding/ processing of secretory proteins such as thyroglobulin and immunoglobulin chains (14,19), suggesting that it may be involved in protein/peptide import into the ER (20)(21)(22)(23).…”

Bn80927

“…These cells are refractory to numerous DNAtargeted agents that are active only on proliferating cells. In cultured cell lines, accumulation of cells in G 0 -G 1 phase of the cell cycle has been reproduced by cell exposure to several stressor agents, including glucosamine (41,42). In such an in vitro model of stress-induced G 0 -G 1 cell cycle arrest, tumor cells remain sensitive to BN80927, whereas CPT, SN38, and VP-16 are devoid of activity.…”