8406

SRPX

DRS|ETX1|SRPX1;sushi-repeat containing protein, X-linked;SRPX;sushi-repeat containing protein, X-linked

sushi repeat-containing protein SRPX|sushi-repeat-containing protein, X chromosome|sushi-repeat-containing protein, X-linked

Xp21.1

protein-coding

Count: 2; Pubmed_search,Generif

Neuroendocrine tumors in the lung fall into four categories: typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC), in ascending order of malignancy. The drs gene was originally isolated as a suppressor against v-src transformation and was shown to induce apoptosis in human cancer cells. The expression of drs was markedly downregulated in various human cancer tissues and cell lines. Furthermore, drs knockout mice showed a tumor-prone phenotype, indicating that drs acts as a tumor suppressor gene in malignant tumor formation. To clarify the role of the drs gene in the development of human pulmonary neuroendocrine tumors, we examined the expression of drs mRNA in tissue specimens from 3 cases of TC, 4 cases of AC, 2 cases of LCNEC, and 11 cases of SCLC by in situ mRNA hybridization. Four cases of normal lung and bronchial epithelia, 8 samples of normal brain tissue, and 2 cases of tumorlets in the lung were also examined. The drs mRNA was definitely expressed in all normal tissues of the lung and brain, and 3 TC and 2 tumorlet tissues. The expression of drs mRNA was also detected in 2 of 2 LCNEC tissues and 3 of 4 AC tissues, although the signals were weak. On the other hand, drs mRNA was not detected in 10 of 11 SCLC tissues. Downregulation of drs mRNA was also observed in 3 of 4 SCLC cell lines that were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Neither gross deletion nor rearrangement of the drs genome was detected in these cell lines by Southern blot analysis. Our results indicate that the downregulation of drs is correlated with the development of SCLC, a highly malignant pulmonary neuroendocrine tumor.

The drs gene was originally isolated as a transformation suppressor gene against the v-src oncogene. expression of drs mRNA is down-regulated by retroviral oncogenes such as v-src and v-K-ras in the rat cell line F2408. expression of drs mRNA is also markedly reduced in a variety of human cancer cell lines, including those of carcinomas of the colon, bladder, and ovary, suggesting that down-regulation of drs mRNA is correlated with the development of human cancers. To clarify the correlation between down-regulation of the drs gene and malignant tumor formation in human colorectal neoplasms, we examined expression of drs mRNA in a variety of colon cancer tissues by in situ hybridization. A total of 53 morphologically distinct neoplastic specimens were divided into the following five groups according to morphology: low and high grade adenoma in 7 and 12 cases, respectively (groups A, B), protruded-type carcinoma in 16 (group C), superficial-type carcinoma with an adenomatous component in 10 (group D) or superficial-type carcinomas without any adenomatous component in 8 (group E). expression of drs mRNA was detected in normal mucosa, low-grade adenoma and most superficial-type carcinomas without any adenomatous component. On the other hand, the rate of drs mRNA expression was significantly lower in protruded-type adenocarcinoma and superficial-type carcinoma with an adenomatous component. Our results indicate that down-regulation of drs mRNA is closely correlated with carcinomas which arise from adenomatous polyps in the course of the adenoma-carcinoma sequence, but that most carcinomas arising de novo are independent of the tumor suppressor function of the drs gene.

The drs gene is an apoptosis-inducing tumor suppressor. By using drs-knockout (KO) mouse embryonic fibroblasts (MEFs), we showed that drs is involved in the host defense against viral infection. In drs-KO MEFs infected with vesicular stomatitis virus, the viral replication and protein synthesis were markedly enhanced without the upregulation of the cellular protein synthesis. Phosphorylation of S6K, S6, 4EBP1 and TSC2 proteins was closely correlated with the enhanced viral replication in drs-KO MEFs. Drs protein could associate with stress-inducible GADD34 to form a complex with TSC1/2, which suppresses mTOR activity. These findings indicate that Drs suppresses viral replication via mTOR-dependent pathway.CI - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.

The drs gene is an apoptosis-inducing tumor suppressor. Previously, we showed that drs contributes to the suppression of tumor formation by generating drs-knockout mice. In this study, by using drs KO mouse embryonic fibroblasts, we found that drs is involved in the autophagy regulation under low serum culture conditions. Both electron microscopy and GFP-LC3 analyses demonstrated that drs is involved in the maturation process of autophagy from autophagosomes to autolysosomes. In addition, drs could associate with Rab24 and the association between drs and Rab24 was enhanced during autophagy. Drs was also co-localized with Rab24 on punctuated structures during autophagy.

The drs gene was isolated as a transformation suppressor against the v-src oncogene. Drs protein has a transmembrane domain and three consensus repeats (CRs) called Sushi motifs in the extracellular domain. The drs gene also has the ability to suppress anchorage-independent growth of human cancer cell lines. In this paper, we report the isolation of a novel variant cDNA of mouse drs (mDRS-2) containing two CRs, in addition to a mouse homolog of drs (mDRS-1) containing three CRs. We investigated the suppressor function of these mDRS cDNAs in human cancer cells and found that the lack of one CR is critical for suppression of anchorage-independent growth by drs.