The Change In Expression Of Very Low Density Lipoprotein Receptor Subtypes During The Induction Of Gastric Adenocarcinoma Cells With All-trans Retinoic Acid

The very low density lipoprotein receptor (VLDLR) is a member of LDL super family, and is the main receptor with which cells can take up the triacylglycerol-rich lipoprotein and participate in triglyceride metabolism. But the recent research found that VLDLR is multifunctional receptor that is similar to the other member of LDLR family, and likes a swiss knife. VLDLR plays an important biological role in growth and development of tissues, cell differentiation, nerve cell location and carcinoma metastasis etc. VLDLR are divided into two subtypes according to the presence of O-linked sugar region located in the outside of the VLDLR's membrane: Type I VLDLRs contain the O-link sugar domain, Type II VLDLRs lack this domain. The results from the present investigation suggest that the expression of VLDLR subtypes is correlated to tissue differentiation and development. Previous researches showed that the expression of type II VLDLR is increased in the chick embryo and early stages of human tissue development; but type I VLDLR is mainly presented in the mature normal tissue cells, and type II VLDLR is low. Particularly, Nakamura et al found that type II VLDLR is the major receptor in the early phase of fetal brain development, and that type I VLDLR is mainly presented in adult brain. It was shown that type II VLDLR is abundantly expressed in poorly-differentiated gastroenteric carcinoma and embryonic intestinal tissue. The recent study found that the expression of VLDLR subtypes is relating to the differentiation of carcinoma cells. Our previous research suggested that type II VLDLR is predominantly expressed in poorly- or moderately-differentiated gastric adenocarcinoma cell lines, whereas type I VLDLR is mainly detected in well-differentiated gastric adenocarcinoma cells. To confirm this phenomenon, this study intend to examine the change on the expression of VLDLR isoforms by inducing the differentiation of tumor cells. The study is aimed to investigate the effect of all-trans retinoic acid(ATRA) on the expression of very low density lipoprotein receptor(VLDLR) subtypes during the induction of gastric adenocarcinoma cell line SGC-7901. SGC-7901 cells were induced with ATRA at final concentration of 0.5μmol/L in the study. Telomerase reverse transcriptase(hTERT) as the symbol of cell differentiation was detected by RT-PCR. Every five passages, cell proliferation was evaluated using the MTT assay, and total RNA and protein were isolated for RT-PCR and Western blot to analyze the expression of VLDLR. The results discovered as following: Both cell proliferation and hTERT mRNA were decreased in the presence of ATRA. The ratio of type I VLDLR to type II VLDLR was increased in both levels of mRNA and protein. Two isoforms of VLDLR mRNA were elevated in time-dependent manner, and there was not significant change in the expression of type I VLDLR protein, but type II VLDLR protein was decreased. This result shows that during the induction with 0.5μmol/L ATRA, the expression of VLDLR subtypes in gastric adenocarcinoma cell line SGC-7901 could be correlated to cell differentiation.In conclusion, the variation of VLDLR subtypes expression during the induction is accord with the distribution of VLDLR subtypes in various differentiated gastric adenocarcinoma cells. These results indicate that VLDLR plays an unknown and important role in the differentiation of cancer cells. These might be the causes of the discrepancy of ligand binding, signalong pathway and subsequent biological effect between two isoforms of VLDLR suitable to the differentiation of cancer cells. However, all needs to be further investigated.