Numb protein expression correlates with a basal-like phenotype and cancer stem cell markers in primary breast cancer

Rennstam, Karin; McMichael, Nicole; Berglund, Pontus; Honeth, Gabriella; Hegardt, Cecilia; Rydén, Lisa; Luts, Lena; Bendahl, Pär‐Ola; Hedenfalk, Ingrid

doi:10.1007/s10549-009-0568-x

Cited by 70 publications

(55 citation statements)

References 27 publications

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“…Decreased expression of Numb, resulting in activation of the proto-oncogene Notch1 and reduction of the tumor suppressor p53, has been demonstrated in breast cancers. Rennstam et al [32] demonstrated that the retained Numb expression was significantly correlated with ER and PR positivity, whereas Numb expression was reduced in the basal-like subtype, and there was an inverse correlation between the Numb expression levels and the CD44+CD24– CSC phenotype in breast tumors. The expression of Notch2 differed in subgroups of breast tumors by genotypes of the breast cancer-associated SNPrs11249433 [30], and Notch3 expression in breast cancer cells was stimulated by TGF beta 1, which is a major prometastatic product of osteoblasts, suggesting an association with bone metastasis [33].…”

Section: Discussionmentioning

confidence: 99%

Characteristic Genes in Luminal Subtype Breast Tumors with CD44+CD24–/Low Gene Expression Signature

Tsunoda

Sakamoto²,

Sawada³

et al. 2011

Oncology

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Objective: Breast cancer cells with CD44+CD24–/low gene expression signature have been suggested to have stem cell-like tumor-initiating properties. The purpose of this study is to clarify the gene expression profiling of cells with CD44+CD24–/low gene expression signature in the luminal subtype. Methods: Laser capture microdissection was used to select the isolation of cancer cells in 35 frozen tissues of breast cancer, and RNA extracted from these cells was examined by real-time RT-PCR to quantify CD44 and CD24 expressions. Human stem cell RT² Profiler PCR Array was used for gene expression analysis in the groups of CD44+CD24–/low and CD44+CD24+ gene expression signature. Results: Thirty-five tumors were divided into 3 groups. Group A was composed of the CD44+CD24–/low type, in which the ratio of CD44/CD24 was >10.0. Group B was composed of the CD44+CD24+ type, in which the ratio was >0.1 and ≤10.0. In group C, composed of the CD44–/lowCD24+ type, the ratio was <0.1. The number of tumors in groups A, B, and C were 5, 28, and 2, respectively. Regarding the correlation of CD44/CD24 status with tumor characteristics, the tumors of group A were significantly associated with axillary lymph node metastasis compared with those of group B (p = 0.033). There were no significant differences in tumor size, nuclear grade, or HER2 status between the two groups. According to signaling pathways, the number of expression genes for the Notch pathway in group A was significantly greater than in group B (p = 0.028). Overexpressed genes for ALDH1 (p = 0.021) and SOX2 (p = 0.018) were noted in group A compared to group B. Conclusion: This study suggests that the Notch pathway may be an important signaling pathway in luminal subtype with CD44+CD24–/low gene expression signature. In addition, either ALDH1 or SOX2 may be a candidate marker for cancer stem cells in luminal subtype breast cancer.

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Section: Discussionmentioning

confidence: 99%

Characteristic Genes in Luminal Subtype Breast Tumors with CD44+CD24–/Low Gene Expression Signature

Tsunoda

Sakamoto²,

Sawada³

et al. 2011

Oncology

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“…This suggests that NOS2 is a novel candidate prognostic marker for basal-like breast cancer and possibly a therapeutic target, whose activity could be selectively inhibited. Recently, increased expression of stem cell markers in basal-like tumors has been reported (40,64). Among them was CD44, which is the major receptor for hyaluronan.…”

Section: Figurementioning

confidence: 99%

Increased NOS2 predicts poor survival in estrogen receptor–negative breast cancer patients

Glynn¹,

Boersma²,

Dorsey³

et al. 2010

J. Clin. Invest.

219

316

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“…NUMB is an important negative regulator of NOTCH signalling (Pece 2004, Stylianou 2006 and expression of NUMB is up-regulated by androgen signalling in myeloblast and muscle cells (Kovacheva et al 2010, Liu et al 2012, further highlighting integration of NOTCH and androgen pathways. Loss of NOTCH control by NUMB has been implicated in promoting a basal-like phenotype in human breast cancer (Pece 2004, Rennstam et al 2009), as has the stabilisation of p53 in response to NUMB (Colaluca et al 2008) (Fig. 5).…”

Section: Integration Of Notch and Armentioning

confidence: 99%

Bringing androgens up a NOTCH in breast cancer

Tarulli

Butler

Tilley

et al. 2014

Endocrine-Related Cancer

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While it has been known for decades that androgen hormones influence normal breast development and breast carcinogenesis, the underlying mechanisms have only been recently elucidated. To date, most studies have focused on androgen action in breast cancer cell lines, yet these studies represent artificial systems that often do not faithfully replicate/ recapitulate the cellular, molecular and hormonal environments of breast tumours in vivo. It is critical to have a better understanding of how androgens act in the normal mammary gland as well as in in vivo systems that maintain a relevant tumour microenvironment to gain insights into the role of androgens in the modulation of breast cancer development. This in turn will facilitate application of androgen-modulation therapy in breast cancer. This is particularly relevant as current clinical trials focus on inhibiting androgen action as breast cancer therapy but, depending on the steroid receptor profile of the tumour, certain individuals may be better served by selectively stimulating androgen action. Androgen receptor (AR) protein is primarily expressed by the hormone-sensing compartment of normal breast epithelium, commonly referred to as oestrogen receptor alpha (ERa (ESR1))-positive breast epithelial cells, which also express progesterone receptors (PRs) and prolactin receptors and exert powerful developmental influences on adjacent breast epithelial cells. Recent lineage-tracing studies, particularly those focussed on NOTCH signalling, and genetic analysis of cancer risk in the normal breast highlight how signalling via the hormone-sensing compartment can influence normal breast development and breast cancer susceptibility. This provides an impetus to focus on the relationship between androgens, AR and NOTCH signalling and the crosstalk between ERa and PR signalling in the hormone-sensing component of breast epithelium in order to unravel the mechanisms behind the ability of androgens to modulate breast cancer initiation and growth.

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Numb protein expression correlates with a basal-like phenotype and cancer stem cell markers in primary breast cancer

Abstract: Decreased expression of Numb, resulting in activation of the proto

Cited by 70 publications

References 27 publications

Characteristic Genes in Luminal Subtype Breast Tumors with CD44+CD24–/Low Gene Expression Signature

Characteristic Genes in Luminal Subtype Breast Tumors with CD44+CD24–/Low Gene Expression Signature

Increased NOS2 predicts poor survival in estrogen receptor–negative breast cancer patients

Bringing androgens up a NOTCH in breast cancer

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