Insulin receptor is expressed in normal canine mammary gland and benign adenomas but decreased in metastatic canine mammary carcinomas similar to human breast cancer

Klopfleisch, Robert; Hvid, Henning; Klose, P.; Costa, A. da; Gruber, Achim D.

doi:10.1111/j.1476-5829.2009.00232.x

Cited by 19 publications

(12 citation statements)

References 29 publications

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“…Of interest qPCR analyses confirmed the differences in mRNA expression levels in metastatic and non-metastatic carcinomas although the fold change in expression difference consistently lower in the qPCR assays when compared with microarray assays for all eight genes analyzed. The eight genes, AURKA, ALOX12, BMP6, ERBB4, HEPACAM2, IGFR2, RAD51, TGFBR3 , were selected due to their description in the literature on canine mammary tumors before[17,21-24,51]. Their gene expression has been described metastatic carcinomas, metastases, adenomas and normal mammary gland and these studies showed a similar tendency of changes in gene expression between benign and malignant canine mammary tissue types[17,21-24,51].…”

Section: Discussionmentioning

confidence: 99%

“…The eight genes, AURKA, ALOX12, BMP6, ERBB4, HEPACAM2, IGFR2, RAD51, TGFBR3 , were selected due to their description in the literature on canine mammary tumors before[17,21-24,51]. Their gene expression has been described metastatic carcinomas, metastases, adenomas and normal mammary gland and these studies showed a similar tendency of changes in gene expression between benign and malignant canine mammary tissue types[17,21-24,51]. Of note, a comparison of the proteome of the same subset of tumours did not identify similar proteins[52].…”

Section: Discussionmentioning

confidence: 99%

“…To this end, established qPCR assays for eight genes that were identified in the metastatic gene signature were used to compare mRNA expression levels in metastatic and non-metastatic tumors. Primer sequences, product length and sequence accession numbers for the PCR assays for AURKA, ALOX12, BMP6, ERBB4, HEPACAM2, IGFR2, RAD51, TGFBR3 and the housekeeper genes A5B, HPRT and RP32 mRNA expression levels were used before [17,21-24] and are describe in Additional file 1. Each qPCR reaction had a 20 μl reaction volume containing 5 μl cDNA corresponding to 100 ng input RNA, 500 nM of each forward and reverse primer, 12.5 μl of the Maxima Sybr Green/Rox qPCR Master Mix (Fermentas, Germany) containing 2.5 mM Mg 2+ and 5 mM dNTP.…”

Section: Methodsmentioning

confidence: 99%

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Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

et al. 2010

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BackgroundSimilar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent.MethodsMessenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer.ResultsMetastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors.ConclusionsMetastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

et al. 2010

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“…However, some studies show that the expression of IGF-II and IGF2R is strongly decreased in carcinomas and metastatic breast cancer, but increased in normal gland and adenomas (23). M6P/IGF2R reduces tumorigenicity and invasive potential of HCC, but knockdown of M6P/IGF2R enhances cell motility and invasiveness (24).…”

Section: Discussionmentioning

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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“…A similar decreased receptor expression with increasing malignancy has been described in several canine tumors before, including the serotonin receptor on canine MCT and several growth factor receptors on metastatic canine mammary carcinomas. 8,[20][21][22] This down-regulation of mostly proliferative but also inhibitory receptors therefore seems to be a common mechanism in canine tumors and reflects the increasing independency of malignant tumors from external proliferation stimuli when compared with benign tumor variants or nonneoplastic cells.…”

Section: Discussionmentioning

confidence: 99%

CD25 Is Expressed by Canine Cutaneous Mast Cell Tumors but not by Cutaneous Connective Tissue Mast Cells

2012

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Canine cutaneous mast cell tumors (MCT) of different histological grades have distinct biological behaviors. However, little is known about underlying molecular mechanisms that lead to tumor development and increasing malignancy with higher tumor grade. Recent studies have identified the interleukin-2 receptor (IL-2R) subunits CD25 and CD2 as markers that distinguish nonneoplastic from neoplastic mast cells in human systemic mastocytosis. In this study, their potential as a marker for canine MCT and their possible impact on MCT carcinogenesis were evaluated. mRNA expression levels of both genes were compared between grade 1 ( n = 12) and grade 3 ( n = 8) MCT, and protein expression levels of CD25 were compared in 90 MCT of different tumor grades. mRNA expression levels of both CD25 and CD2 were upregulated in grade 3 MCT. In contrast, CD25 protein was expressed by fewer tumor cells and at decreased levels in grade 3 tumors, while most grade 1 MCT had strong CD25 protein expression. Moreover, CD25 was not expressed by nonneoplastic, resting cutaneous mast cells, while few presumably activated mast cells in tissue samples from dogs with allergic dermatitis had weak CD25 expression. Taken together, these findings suggest that CD25 may play a critical role in early MCT development and may be a stimulatory factor in grade 1 MCT, while grade 3 MCT seem to be less dependent on CD25. Because of the low number of CD25-positive tumor cells in high-grade tumors, the usefulness of CD25 as a tumor marker is, however, questionable.

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Insulin receptor is expressed in normal canine mammary gland and benign adenomas but decreased in metastatic canine mammary carcinomas similar to human breast cancer

Cited by 19 publications

References 29 publications

Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

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

CD25 Is Expressed by Canine Cutaneous Mast Cell Tumors but not by Cutaneous Connective Tissue Mast Cells

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