Pituitary adenomas（PAs） are well known as a common intracranial benign tumor, and a portion of PAs are refractory to current therapeutic methods. Erb B receptors family signaling pathway regulates the expression of ...Pituitary adenomas（PAs） are well known as a common intracranial benign tumor, and a portion of PAs are refractory to current therapeutic methods. Erb B receptors family signaling pathway regulates the expression of PAs activation associated gene. Inhibition of epidermal growth factor receptor（EGFR） can inhibit proliferation of PAs. Leucine-rich repeats and immunoglobulin-like domains protein 1（ LRIG1）, a negative mediated gene of Erb B receptors family, plays a role in many tumors. However, there are seldom researches about the functional role of LRIG1 in PAs. The aim of this study is to explore the potential effect of LRIG1 and its regulating mechanism in PAs. First, we investigated the role of LRIG1 in cell migration, invasion of PAs with transfected LRIG1 or control. Then, we explored its impact on cell proliferation and apoptosis of PAs in vivo. To study the regulating mechanism of LRIG1, we examined the expression of molecular factor of PI3K/AKT and Ras/Raf/ERK pathway using Western blotting in vitro and RT-PCR in vitro and in vivo. It was found that LRIG1 over-expression inhibited cell migration, invasion and proliferation, and promoted apoptosis of PAs in vivo and in vitro. Furthermore, LRIG1 suppressed the expression of signaling of PI3K/AKT and Ras/Raf/ERK pathways in PAs. LRIG1, as a negative mediated gene of tumor, can inhibit biological function of PAs via inhibiting PI3K/AKT and Ras/Raf/ERK pathways, and it might be a new target for gene therapy of PAs.展开更多
Objective： LRIG1 gene is a newly found human gene that displays homologies to the Drosophila Kek-1 gene. Previous researches have shown that the LRIG1 gene almost expressed in all human tissues. However, its function...Objective： LRIG1 gene is a newly found human gene that displays homologies to the Drosophila Kek-1 gene. Previous researches have shown that the LRIG1 gene almost expressed in all human tissues. However, its functions, particularly its functions in human tumors, are still unknown. The goals of the present study are to magnify the expression spectrum of the LRIG1 gene and determine their roles in the oncogenesis. Methods： A triphasic oligonucleotide probe was designed and used to detect the expression level of the LRIG1 gene in 16 astrocytomas and the corresponding tissues around the tumors by in situ hybridization. 11 primary astrocytoma cells were cultured. Among these, the expression level of the LRIG1 gene was checked by in situ hybridization and the expression of the Proliferating Cell Nuclear Antigen （PCNA） protein was detected by immunohistochemistry. Results： The expression of LRIG1 protein was detected in different degree in all the tumors and the surrounding tissues. Compared to the surrounding tissues, the expression of the tumors was lower. The decrease extends from the surrounding tissues to the tumors were correlation to the tumors＇ grades. The primary cultured cells also expressed LRIG1 to various extent and the expression of LRIG1 in the cultures was negatively correlated with the intensity of the PCNA staining. Conclusion： The LRIG1 protein may inhibit the growth of tumors of glial cells and the down-regulation of the LRIG1 gene may be involved in the development and progression of the tumor.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81560412)Jiangxi Provincial Health Development Planning Commission Project(No.20141065)Jiangxi Provincial Natural Science Foundation of China(No.20152BCB24009 and No.20151BDH80009)
文摘Pituitary adenomas（PAs） are well known as a common intracranial benign tumor, and a portion of PAs are refractory to current therapeutic methods. Erb B receptors family signaling pathway regulates the expression of PAs activation associated gene. Inhibition of epidermal growth factor receptor（EGFR） can inhibit proliferation of PAs. Leucine-rich repeats and immunoglobulin-like domains protein 1（ LRIG1）, a negative mediated gene of Erb B receptors family, plays a role in many tumors. However, there are seldom researches about the functional role of LRIG1 in PAs. The aim of this study is to explore the potential effect of LRIG1 and its regulating mechanism in PAs. First, we investigated the role of LRIG1 in cell migration, invasion of PAs with transfected LRIG1 or control. Then, we explored its impact on cell proliferation and apoptosis of PAs in vivo. To study the regulating mechanism of LRIG1, we examined the expression of molecular factor of PI3K/AKT and Ras/Raf/ERK pathway using Western blotting in vitro and RT-PCR in vitro and in vivo. It was found that LRIG1 over-expression inhibited cell migration, invasion and proliferation, and promoted apoptosis of PAs in vivo and in vitro. Furthermore, LRIG1 suppressed the expression of signaling of PI3K/AKT and Ras/Raf/ERK pathways in PAs. LRIG1, as a negative mediated gene of tumor, can inhibit biological function of PAs via inhibiting PI3K/AKT and Ras/Raf/ERK pathways, and it might be a new target for gene therapy of PAs.
文摘Objective： LRIG1 gene is a newly found human gene that displays homologies to the Drosophila Kek-1 gene. Previous researches have shown that the LRIG1 gene almost expressed in all human tissues. However, its functions, particularly its functions in human tumors, are still unknown. The goals of the present study are to magnify the expression spectrum of the LRIG1 gene and determine their roles in the oncogenesis. Methods： A triphasic oligonucleotide probe was designed and used to detect the expression level of the LRIG1 gene in 16 astrocytomas and the corresponding tissues around the tumors by in situ hybridization. 11 primary astrocytoma cells were cultured. Among these, the expression level of the LRIG1 gene was checked by in situ hybridization and the expression of the Proliferating Cell Nuclear Antigen （PCNA） protein was detected by immunohistochemistry. Results： The expression of LRIG1 protein was detected in different degree in all the tumors and the surrounding tissues. Compared to the surrounding tissues, the expression of the tumors was lower. The decrease extends from the surrounding tissues to the tumors were correlation to the tumors＇ grades. The primary cultured cells also expressed LRIG1 to various extent and the expression of LRIG1 in the cultures was negatively correlated with the intensity of the PCNA staining. Conclusion： The LRIG1 protein may inhibit the growth of tumors of glial cells and the down-regulation of the LRIG1 gene may be involved in the development and progression of the tumor.
