ICSBP-mediated immune protection against BCR-ABL–induced leukemia requires the CCL6 and CCL9 chemokines

Nardi, Valentina; Naveiras, Olaia; Azam, Mohammad; Daley, George Q.

doi:10.1182/blood-2008-07-167189

Cited by 28 publications

(26 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We found that transcripts of CCL5, CCL9 and CXCL10 increased 12-, 6.8-, and 4.5-fold, respectively, in Colon26L5-CUG2 cells compared to those in Colon26L5-Vec cells (data not shown). Many lines of evidence have supported that CCL5, CCL9 and CXCL10 are involved in metastasis of various cancer cells (27)(28)(29), and have shown that IFN signaling induces upregulation of these chemokines (30)(31)(32). We therefore assume that upregulated chemokines through the STAT1-IFN axis enhance migration of colon cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Cancer upregulated gene 2, a novel oncogene, enhances migration and drug resistance of colon cancer cells via STAT1 activation

Malilas¹,

Koh²,

Kim³

et al. 2013

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Cancer upregulated gene (CUG) 2, as a novel oncogene, has been predominantly detected in various cancer tissues, such as ovary, liver, lung and colon. We recently showed that CUG2 elevates STAT1 activity, leading to resistance to infection by oncolytic vesicular stomatitis virus. To investigate a possible role for CUG2-induced activation of STAT1 in oncogenesis, we first established a colon cancer cell line stably expressing CUG2 (Colon26L5-CUG2). Colon26L5-CUG2 exhibited higher levels not only in phosphorylation of STAT1, but also phosphorylation of Jak1/Tyk2 compared to that of the control (Colon26L5-Vec) cell line. Inhibition of Akt or ERK activity reduced phosphorylation of STAT1 in Colon26L5-CUG2 cells whereas inhibition of p38 MAPK did not significantly decrease levels of STAT1 phosphorylation, indicating that cell proliferation signals may be involved in CUG2-mediated activation of STAT1. Suppression of STAT1 expression diminished cell migration and wound healing compared to the control cells. In addition, since CUG2 expression conferred resistance to DNA damage caused by doxorubicin treatment, we investigated whether STAT1 is involved in resistance to doxorubicininduced cell death. We found that STAT1 was not activated in Colon26L5-Vec cells while phosphorylated STAT1 was maintained in Colon26L5-CUG2 cells during doxorubicin treatment. Furthermore, suppression of STAT1 expression sensitized Colon26L5-CUG2 cells to doxorubicin-induced apoptosis whereas the control cells exhibited resistance to doxorubicin. Taken together, our results suggest that CUG2 enhances metastasis and drug resistance through STAT1 activation, which eventually contributes to tumor progression. IntroductionTo discover new genes that play a crucial role in common tumorigenesis regardless of tissue origin, we analyzed commonly upregulated unknown genes in 242 normal and 300 tumor samples originating from 11 different tissues using the Affymetrix gene chip system. An Affymetrix fragment, later named cancer upregulated gene (CUG) 2 was identified as a candidate gene that is commonly upregulated in various tumor tissues such as ovary, liver, lung and colon. This CUG2 was mapped to chromosome 6q22.32; it spans ~8.5 kb with a three-exon structure and encodes a 88-amino acid polypeptide (1). Further study has revealed that CUG2 is a new component of centromere required for a proper kinetochore function during cell division (2). Of interest, CUG2 has been shown to harbor an oncogenic effect in a transplanted model using NIH3T3 cells expressing CUG2, in a manner similar to Ras (1). Although CUG2 overexpression leads to activated Ras and MAPKs including p38 MAPK, which eventually facilitates oncolytic reoviral replication (3), CUG2 contrastingly provides resistance to oncolytic vesicular stomatitis virus infection through activation of STAT1 as shown in our recent study (4).Although STAT1 is well known as a master transcription factor for IFN-related intracellular signaling, leading to antiviral activity, several lines of evidence hav...

show abstract

Section: Discussionmentioning

confidence: 99%

Cancer upregulated gene 2, a novel oncogene, enhances migration and drug resistance of colon cancer cells via STAT1 activation

Malilas¹,

Koh²,

Kim³

et al. 2013

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…GP49B is a member of the immunoglobulin superfamily and has a regulatory role in T-cell priming (36). CCL9 is an interferon-␥-inducible ␤-chemokine and has shown potent antitumor activity through attraction of cytotoxic T lymphocytes and inhibition of angiogenesis (32,56). The C/EBP␣ is required for the maintenance of CCL9 in transformation of hematopoietic cells by the BCR/ABL oncogene (32).…”

Section: Discussionmentioning

confidence: 99%

Mammary gland morphological and gene expression changes underlying pregnancy protection of breast cancer tumorigenesis

Misra¹,

Bentley²,

Bond³

et al. 2012

Physiological Genomics

View full text Add to dashboard Cite

A full-term pregnancy early in life reduces lifetime risk of developing breast cancer, and the effect can be mimicked in rodents by full-term pregnancy or shortterm treatment with exogenous estrogen and progesterone. To gain insight into the protective mechanism, 15 3-mo-old postpubertal virgin Lewis rats were randomly assigned to three groups: control (C), pregnancy (P), or hormone (H). The P group animals underwent a full-term pregnancy, and H group animals were implanted subcutaneously with silastic capsules filled with ethynyl estradiol and megesterol acetate for 21 days. C and P animals were implanted with sham capsules. On day 21 capsules were removed, which was followed by a 49-day involution period, euthanasia, and mammary tissue collection. Global gene expression was measured using Rat Genome 230.2 Arrays. Histological analysis revealed that P and H treatments induced sustained morphological changes in the mammary gland with significantly increased percentages of mammary parenchyma and stromal tissues and higher ratio of stroma to parenchyma. Transcriptome analysis showed that P and H treatments induced sustained global changes in gene expression in the mammary gland. Analysis of commonly up-and downregulated genes in P and H relative to C treatment showed increased expression of three matrix metallopeptidases (Mmp3, 8, and 12), more differentiated mammary phenotype, enhanced innate and adaptive immunity, and reduced cell proliferation and angiogenic signatures. The sustained morphological and global gene expression changes in mammary tissue after pregnancy and hormone treatment may function together to provide the protective effect against breast cancer. breast cancer protection; hormone; pregnancy BREAST CANCER IS ONE OF THE most common cancers in women and affects nearly 10% of all women in US. In the year 2009, 192,370 new cases of invasive and 62,280 new cases of in situ breast cancer were estimated to have occurred, with 40,170 estimated deaths (3). Various epidemiological studies have revealed that multiple factors including hormones, genetics, reproductive history, radiation, socio-economic status, place of residence, ethnicity, and the environment affect the incidence of breast cancer (9,19,28,29,50,51,60). It has been shown that full-term pregnancy early in life has a protective effect on women against the risk of breast cancer irrespective of genetic background, age, race, or ethnic background (2,37,39,40,64,65,72). For instance, Lambe et al. (1996) (39, 40) and Albrektsen et al. (2005) (2) reported that full-term gestation in a woman younger than 24 yr of age reduces her lifetime risk of developing breast cancer, and this parity-induced protection against breast cancer is significantly affected by the total number of pregnancies. The epidemiological data on breastfeeding and breast cancer risk in humans also show that prolonged breast-feeding confers additional protection against breast cancer (17). However, aborted pregnancies are not associated with decreased risk for breast cancer (8).A ...

show abstract

“…However, IRF8 appears to exert its anti-leukemic activity also by modulating immunity. The coexpression of IRF8 in a BCR-ABL-transformed mouse pro-B cell line induces a CD8 + cytotoxic T cell response that prevents the in vivo establishment of leukemia in a CCL6-and CCL9-dependent manner [70,71]. Indeed, it has long been suggested that CML is highly sensitive to T cell-mediated tumor immunity.…”

Section: As Already Mentioned Irf8mentioning

confidence: 99%

Regulation of myelopoiesis by the transcription factor IRF8

2015

View full text Add to dashboard Cite

ICSBP-mediated immune protection against BCR-ABL–induced leukemia requires the CCL6 and CCL9 chemokines

Cited by 28 publications

References 50 publications

Cancer upregulated gene 2, a novel oncogene, enhances migration and drug resistance of colon cancer cells via STAT1 activation

Cancer upregulated gene 2, a novel oncogene, enhances migration and drug resistance of colon cancer cells via STAT1 activation

Mammary gland morphological and gene expression changes underlying pregnancy protection of breast cancer tumorigenesis

Regulation of myelopoiesis by the transcription factor IRF8

Contact Info

Product

Resources

About