Simultaneous evaluation of maspin and CXCR4 in patients with breast cancer

Tsoli, Efthymia; Tsantoulis, Petros; Papalambros, Alexandros; Perunovic, Branko; England, David; Rawlands, David A; Reynolds, Gary; Vlachodimitropoulos, Dimitrios; Morgan, Susan; Spiliopoulou, Chara; Athanasiou, Thanos; Gorgoulis, Vassilis G.

doi:10.1136/jcp.2006.037887

Cited by 20 publications

(17 citation statements)

References 43 publications

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“…Our finding that maspin transcripts also were elevated in NRL-PRL glands is in seeming conflict with the portrait of this gene as a tumor suppressor (Barsky & Karlin 2005; Bailey et al 2006). However, recent reports indicate that elevated maspin mRNA may be a negative prognostic indicator for patients with node negative breast cancer (Bieche et al 2003; Tsoli et al 2007), suggesting a more complicated biological role for this protein. Interestingly, other transcripts elevated in myoepithelial cells of DCIS lesions in women (Polyak & Hu 2005), including IGF-2, SOCS-3 and the AP-1 proteins, JunD and c-Fos, have been reported to be elevated by PRL at mammary targets (Tam et al 2001; Brisken et al 2002; Hovey et al 2003; Gutzman et al 2004b).…”

Section: Discussionmentioning

confidence: 99%

Ovarian hormones are not required for PRL-induced mammary tumorigenesis, but estrogen enhances neoplastic processes

Arendt¹,

Evans²,

Rugowski³

et al. 2009

Journal of Endocrinology

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Epidemiologic studies have demonstrated that increased prolactin (PRL) exposure raises the risk of invasive estrogen receptor a (ERa)-positive breast cancer in women. However, the mechanism(s) whereby this occurs and the interactions with estrogen itself in this disease remain poorly understood. In order to investigate the role of ovarian hormones in the disease process, we employed a transgenic model neu-related lipocalin (NRL)-PRL in which transgenic PRL is directed to mammary epithelial cells by the PRL-and estrogen-insensitive NRL promoter, mimicking the endogenous PRL expression within the breast observed in women. This high local exposure leads to mammary lesion development and eventually carcinomas. Ovariectomy (ovx), shortly after puberty, did not alter the incidence or latency of PRL-induced mammary carcinomas, consistent with the independence of PRL from circulating estrogens as a risk factor for invasive breast cancer in women. However, chronic estrogen administration to ovx NRL-PRL females decreased the latency of both ERa-positive and -negative tumors. We identified multiple mechanisms that may underlie this observation. Elevated estrogen exposure cooperated with PRL to increase epithelial proliferation and myoepithelial abnormalities, increasing the incidence of preneoplastic lesions. Critical components of the extracellular matrix secreted by the myoepithelium were reduced with age, and transgenic PRL raised transcripts for tenascin-C and maspin, both associated with tumor progression and poor prognosis in subclasses of clinical breast tumors. Mammary pERK1/2 and pAkt, but not phosphorylated Stat5, were markedly elevated by local PRL. Together, these findings indicate that PRL employs multiple mechanisms to promote mammary tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Ovarian hormones are not required for PRL-induced mammary tumorigenesis, but estrogen enhances neoplastic processes

Arendt¹,

Evans²,

Rugowski³

et al. 2009

Journal of Endocrinology

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“…88 A similar line of work followed in the context of BCa, which also metastasizes to bone with high frequency. 89 Early studies documented ectopic expression in prostate cancer and BCa cells of CXCR4, MMPs, OPN, BSP, RANKL 20,90–96 and finally RUNX2, the osteoblast master regulator. 97,98 RUNX2 was shown to prevent prostate cancer cell apoptosis by stimulating the expression of survivin and Bcl2.…”

Section: Oncogenic Properties Of the Runx Family And The Emerging Rolmentioning

confidence: 99%

The RUNX family in breast cancer: relationships with estrogen signaling

Frenkel

2012

Oncogene

109

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The three RUNX family members are lineage specific master regulators, which also have important, context-dependent roles in carcinogenesis as either tumor suppressors or oncogenes. Here we review evidence for such roles in breast cancer (BCa). RUNX1, the predominant RUNX family member in breast epithelial cells, has a tumor suppressor role reflected by many somatic mutations found in primary tumor biopsies. The classical tumor suppressor gene RUNX3 does not consist of such a mutation hot spot, but it too seems to inhibit BCa; it is often inactivated in human BCa tumors and its haploinsufficiency in mice leads to spontaneous BCa development. The tumor suppressor activities of RUNX1 and RUNX3 are mediated in part by antagonism of estrogen signaling, a feature recently attributed to RUNX2 as well. Paradoxically, however RUNX2, a master osteoblast regulator, has been implicated in various aspects of metastasis in general and bone metastasis in particular. Reciprocating the anti-estrogenic tumor suppressor activity of RUNX proteins, inhibition of RUNX2 by estrogens may help explain their context-dependent anti-metastatic roles. Such roles are reserved to non-osseous metastasis, because ERα is associated with increased, not decreased skeletal dissemination of BCa cells. Finally, based on diverse expression patterns in BCa subtypes, the successful use of future RUNX-based therapies will most likely require careful patient selection.

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“…High maspin expression has been associated with high CXCR4 expression in patients with advanced breast cancer. (Tsoli et al, 2007). These findings suggest that compounds that promote the expression of maspin will not only suppress tumor formation but will also inhibit metastasis as an added level of protection.…”

Section: Tumor Suppressorsmentioning

confidence: 84%