Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors

Herschkowitz, Jason I.; Simin, Karl; Weigman, Victor; Mikaelian, Igor; Usary, Jerry; Hu, Zhiyuan; Rasmussen, Karen; Jones, Laundette P.; Assefnia, Shahin; Chandrasekharan, Subhashini; Backlund, Michael G.; Yin, Yuzhi; Khramtsov, Andrey; Bastein, Roy; Quackenbush, John; Glazer, Robert I.; Brown, Powel H.; Green, Jeffrey E.; Kopelovich, Levy; Furth, Priscilla A.; Palazzo, Juan; Olopade, Olufunmilayo I.; Bernard, Philip S.; Churchill, Gary A.; Dyke, Terry Van; Perou, Charles M.

doi:10.1186/gb-2007-8-5-r76

Cited by 1,081 publications

(1,269 citation statements)

References 66 publications

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“…Our results are also in agreement with a recent publication demonstrating the loss of cell adhesion molecules, including claudin-4 and claudin-7, in 4T1 sub-populations that are metastatic to the liver (Erin et al, 2009). Finally, a 'claudin-low' subtype has recently been identified in 13 primary human breast cancers that possess features that are both similar to but distinct from the previously defined basal subtype (Herschkowitz et al, 2007). This subtype is characterized Figure 6 Claudin-2 expression is enriched in human breast cancer liver metastases compared with primary tumors.…”

Section: Discussionsupporting

confidence: 93%

Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes

et al. 2010

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The liver represents the third most frequent site of metastasis in patients with breast cancer. We performed in vivo selection using 4T1 breast cancer cells to identify genes associated with the liver metastatic phenotype. Coincident with the loss of numerous tight-junctional proteins, we observe claudin-2 overexpression, specifically in liver-aggressive breast cancer cells. We further demonstrate that claudin-2 is both necessary and sufficient for the ability of 4T1 breast cancer cells to colonize and grow in the liver. The liver-aggressive breast cancer cells display a claudin-2-mediated increase in their ability to adhere to extracellular matrix (ECM) components, such as fibronectin and type IV collagen. Claudin-2 facilitates these cell/matrix interactions by increasing the cell surface expression of a 2 b 1 -and a 5 b 1 -integrin complexes in breast cancer cells. Indeed, claudin-2-mediated adhesion to fibronectin and type IV collagen can be blocked with neutralizing antibodies that target a 5 b 1 and a 2 b 1 complexes, respectively. Immunohistochemical analyses reveal that claudin-2, although weakly expressed in primary human breast cancers, is readily detected in all liver metastasis samples examined to date. Together, these results uncover novel roles for claudin-2 in promoting breast cancer adhesion to the ECM and define its importance during breast cancer metastasis to the liver.

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Section: Discussionsupporting

confidence: 93%

Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes

et al. 2010

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“…Overrepresentation of c-kit in Brca1-deficient mammary glands is also consistent with the finding that c-kit is overexpressed in a proportion of human and mouse Brca1-associated mammary tumours (Herschkowitz et al, 2007;Lim et al, 2009). This supports our previous hypothesis that luminal progenitor cells, rather than basal or stem cells, are the target of BRCA1-associated tumourigenesis (Lim et al, 2009), which in turn is consistent with our previous studies showing no mammary phenotype when Brca1 is specifically deleted in non-luminal compartments of the mammary gland (Smart et al, 2008).…”

Section: (A) Endogenoussupporting

confidence: 87%

Analysis of Brca1-deficient mouse mammary glands reveals reciprocal regulation of Brca1 and c-kit

et al. 2010

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Disruption of the breast cancer susceptibility gene Brca1 results in defective lobular-alveolar development in the mammary gland and a predisposition to breast tumourigenesis in humans and in mice. Recent evidence suggests that BRCA1 loss in humans is associated with an expansion of the luminal progenitor cell compartment in the normal breast and tumours with a luminal progenitorlike expression profile. To further investigate the role of BRCA1 in the mammary gland, we examined the consequences of Brca1 loss in mouse mammary epithelial cells in vitro and in vivo. Here, we show that Brca1 loss is associated with defective morphogenesis of SCp2 and HC11 mouse mammary epithelial cell lines and that in the MMTV-Cre Brca1 Co/Co mouse model of Brca1 loss, there is an accumulation of luminal progenitor (CD61 þ CD29 lo CD24 þ ) cells during pregnancy. By day 1 of lactation, there are marked differences in the expression of 1379 genes, with most significantly altered pathways and networks, including lactation, the immune response and cancer. One of the most differentially expressed genes was the luminal progenitor marker, c-kit. Immunohistochemical analysis revealed that the increase in c-kit levels is associated with an increase in c-kit positivity. Interestingly, an inverse association between Brca1 and c-kit expression was also observed during mammary epithelial differentiation, and small interfering RNA-mediated knockdown of Brca1 resulted in a significant increase in c-kit mRNA levels. We found no evidence that c-kit plays a direct role in regulating differentiation of HC11 cells, suggesting that Brca1-mediated induction of c-kit probably contributes to Brca1-associated tumourigenesis via another cellular process, and that c-kit is likely to be a marker rather than a mediator of defective lobular-alveolar development resulting from Brca1 loss.

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“…However, whether DPPA still possesses anti‐tumour activity in luminal‐like breast cancer remains to be clarified. The MMTV‐PyMT spontaneous breast cancer transgenic mouse is a well‐characterized model to simulate human luminal‐like breast cancer 18, 19. In this study, MMTV‐PyMT mice and MCF‐7 cells subcutaneous xenograft tumour model mice were employed to elucidate the possible anti‐tumour role of DPPA in luminal‐like breast cancer in vivo.…”

Section: Resultsmentioning

confidence: 99%

Dipalmitoylphosphatidic acid inhibits breast cancer growth by suppressing angiogenesis via inhibition of the CUX1/FGF1/HGF signalling pathway

Chen

Zhou

Yao

et al. 2018

J Cellular Molecular Medi

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Tumour growth depends on a continual supply of the nutrients and oxygen, which are offered by tumour angiogenesis. Our previous study showed that dipalmitoylphosphatidic acid (DPPA), a bioactive phospholipid, inhibits the growth of triple‐negative breast cancer cells. However, its direct effect on angiogenesis remains unknown. Our work showed that DPPA significantly suppressed vascular growth in the chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. Meanwhile, tumour angiogenesis and tumour growth were inhibited by DPPA in the tumour tissues of an experimental breast cancer model, a subcutaneous xenograft mouse model and a genetically engineered spontaneous breast cancer mouse model (MMTV‐PyMT). Furthermore, DPPA directly inhibited the proliferation, migration and tube formation of vascular endothelial cells. The anti‐angiogenic effect of DPPA was regulated by the inhibition of Cut‐like homeobox1 (CUX1), which transcriptionally inhibited fibroblast growth factor 1 (FGF1), leading to the downregulation of hepatocyte growth factor (HGF). This work first demonstrates that DPPA directly inhibits angiogenesis in cancer development. Our previous work along with this study suggest that DPPA functions as an anti‐tumour therapeutic drug that inhibits angiogenesis.

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Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors

Cited by 1,081 publications

References 66 publications

Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes

Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes

Analysis of Brca1-deficient mouse mammary glands reveals reciprocal regulation of Brca1 and c-kit

Dipalmitoylphosphatidic acid inhibits breast cancer growth by suppressing angiogenesis via inhibition of the CUX1/FGF1/HGF signalling pathway

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