Decreased expression of the mannose 6- phosphate/insulin-like growth factor-II receptor promotes growth of human breast cancer cells

Chen, Zhihong; Ge, Yubin; Landman, Natalie; Kang, Jing

doi:10.1186/1471-2407-2-18

Cited by 50 publications

(43 citation statements)

References 36 publications

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“…Our data support findings of IGF2R GSEs in proliferation screen (Primiano et al, 2003) and IGF2R antisense effect on survival of HSV1-infected cells (Zhou and Roizman, 2002). However, IGF2R role as a death receptor for granzyme B during cytotoxic T-cell-induced apoptosis (Motyka et al, 2000), apoptogenic effect of IGF2R overexpression in colon carcinoma SW48 cells (Souza et al, 1999) and cytoprotective effect of IGF2R ribozyme in MCF7 breast carcinoma cells (Chen et al, 2002) appear to be contradictory to our results. A recent study of IGF2R overexpression (Schaffer et al, 2003) reports opposing proliferation phenotypes in different prostate cancer cell lines offering potential explanation for such discrepancy.…”

Section: Discussioncontrasting

confidence: 56%

“…In total 25 genes in this category were identified by two or more putative GSEs (Table 1). We have included in the study the insulin-like growth factor II receptor/mannose-6-phosphate receptor (IGF2R) gene (which yielded a single antisense putative GSE in our apoptosis screen) since it was previously shown to promote apoptosis in different cancer cell models (Souza et al, 1999;Chen et al, 2002).…”

Section: Apoptogenic Gse Screen Hits Derived From the Genes Encoding mentioning

confidence: 99%

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Identification of cell surface and secreted proteins essential for tumor cell survival using a genetic suppressor element screen

Gelman

Stull

et al. 2004

Oncogene

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Survival factors play critical roles in regulating cell growth in normal and cancer cells. We designed a genetic screen to identify survival factors which protect tumor cells from apoptosis. A retroviral expression library of random cDNA fragments was constructed from cancer cells and used to transduce the colon carcinoma cell line HCT116. Recipient cells were functionally selected for induction of caspase 3-mediated apoptosis. Analyses of over 10 000 putative genetic suppression elements (GSEs) sequences revealed cognate gene candidates that are implicated in apoptosis. We further analysed 26 genes encoding cell surface and secreted proteins that can potentially serve as targets for therapeutic antibodies. Tetracycline-inducible GSEs from several gene candidates induced apoptosis in stable HCT 116 cell lines. Similar phenotypes were caused by RNAi derived from the same genes. Our data suggest requirement for the cell surface targets IGF2R, L1CAM and SLC31A1 in tumor cell growth in vitro, and suggests that IGF2R is required for xenograft tumor growth in a mouse model.

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Section: Discussioncontrasting

confidence: 56%

Section: Apoptogenic Gse Screen Hits Derived From the Genes Encoding mentioning

confidence: 99%

Identification of cell surface and secreted proteins essential for tumor cell survival using a genetic suppressor element screen

Gelman

Stull

et al. 2004

Oncogene

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“…M6P/IGF2R is found inactivated in prostate cancer and the mutation of this gene is an early event in the development of prostate cancer (14). M6P/IGF2R also functions as a growth suppressor, but the loss or mutation of this gene contributes to development and progression of some cancers (15,16) and is involved in HBV-associated hepatocarcinogenesis (17). Moreover, M6P/ IGF2R controls cell adhesion and invasion by regulating αv integrin expression and accelerating uPAR cleavage (18), and restricts the metastatic propensity of squamous cell carcinomas (19).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of IGF2R suppresses proliferation and induces apoptosis in hemangioma cells in vitro and in vivo

et al. 2014

International Journal of Oncology

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Abstract. Insulin-like growth factor-II (IGF-II)/IGF2R signaling plays a pivotal role in cell growth, migration and differentiation in many malignancies. An individual with high IGF-II expression levels has a high risk of developing cancer, but IGF2R is often considered to be a tumor suppressor. To date, little has been reported about the role of IGF-II/IGF2R signaling in hemangiomas (HAs). Thus, uncovering the mechanisms of IGF-II/IGF2R signaling is very important to understanding the development of HAs. In the present study, the expression of IGF-II and IGF2R was investigated in 27 cases of HAs of different phases by immunohistochemistry. Through lentivirus-mediated IGF2R siRNA (Lv-siIGF2R) in HA-derived endothelial cells (HDECs), we observed the effects of IGF2R knockdown on the biological behavior of HA cells. We found that the expression of IGF-II and IGF2R was significantly increased in proliferating phase HAs, but decreased in involuting phase HAs. Furthermore, knockdown of IGF2R in vitro significantly diminished the proliferative activity and induced apoptosis and cycle arrest with decreased expression of PCNA, Ki-67, Bcl-2, Cyclin D1 and E and increased the expression of Bax in the proliferative phase HAs (HDEC and CRL-2586 EOMA cells). In addition, the tumor volumes in a subcutaneous HDEC nude mouse model treated with Lv-siIGF2R were significantly smaller than those of the control group. Taken together, our findings indicate that the expression of IGF-II and IGF2R is increased in proliferating phase HAs, and knockdown of IGF2R suppresses proliferation and induces apoptosis in HA cells in vitro and in vivo, suggesting that IGF2R may represent a novel therapeutic target for the treatment of human HAs.

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“…Reduced expression of the receptor produced by various antisense strategies has the opposite effect of increasing cell proliferation and, in some case, reducing apoptosis. Reduced expression was reported to increase growth of JEG-3 cells in vitro and in vivo (O'Gorman et al, 1999) and enhance IGF-IIinduced proliferation and reduce susceptibility to TNFinduced apoptosis in the MCF-7 cells (Chen et al, 2002). While these studies provide information concerning possible roles of the receptor in the development of cancer, they have been carried out using cells with normal levels of the receptor that have acquired tumorigenic and metastatic characteristics through mechanisms other than those involving Man-6-P/IGF-2 expression.…”

Section: Introductionmentioning

confidence: 99%

Demonstration of tumor suppression by mannose 6-phosphate/insulin-like growth factor 2 receptor

Sahagian

2004

Oncogene

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The mannose 6-phosphate/IGF-2 receptor has been proposed to be a tumor suppressor gene on the basis of loss of heterozygosity and mutations in tumors from cancer patients. To test this hypothesis, the receptor was expressed in 66cl4, a mouse mammary tumor cell line deficient in the receptor. Expression of the receptor corrected the abnormal lysosomal trafficking phenotype displayed by these cells. Receptor expression had no apparent effect on growth or invasiveness of the cells in vitro but effectively inhibited formation of mammary tumors in BALB/c mice. Analysis of cell proliferation and apoptosis in tumors indicated that the primary effect of the receptor was to inhibit cell proliferation. Proliferation indices for receptor-deficient and receptor-expressing tumors, as determined by BrdU incorporation, were 24.6 and 7.6%, respectively. No significant effect of receptor expression on apoptosis was observed. Receptor expression similarly inhibited tumor growth in BALB/c scid mice indicating that cytotoxic T cells and other components of the immune system missing in scid mice are not involved in the receptor's tumor suppressing effect. These findings establish a role for the receptor as a bona fide tumor suppressor gene and together with previous studies, suggest an important role for the receptor in human and rodent cancers.

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Decreased expression of the mannose 6- phosphate/insulin-like growth factor-II receptor promotes growth of human breast cancer cells

Cited by 50 publications

References 36 publications

Identification of cell surface and secreted proteins essential for tumor cell survival using a genetic suppressor element screen

Identification of cell surface and secreted proteins essential for tumor cell survival using a genetic suppressor element screen

Knockdown of IGF2R suppresses proliferation and induces apoptosis in hemangioma cells in vitro and in vivo

Demonstration of tumor suppression by mannose 6-phosphate/insulin-like growth factor 2 receptor

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