Signal Transducer and Activator of Transcription-5 Activation and Breast Cancer Prognosis

Nevalainen, Marja T.; Xie, Jianwu; Torhorst, J.; Bubendorf, Lukas; Haas, Philippe; Kononen, Juha; Sauter, Guido; Rui, Hallgeir

doi:10.1200/jco.2004.11.046

Cited by 208 publications

(187 citation statements)

References 22 publications

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“…The role of STAT5 transcription factor in breast tumorogenesis has been underlined in recent studies (29,30). STAT5 appeared to be constitutively phosphorylated in the three cell models expressing PrlR I146L .…”

Section: Discussionmentioning

confidence: 99%

Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors

Bogorad

Courtillot

Mestayer

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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There is currently no known genetic disease linked to prolactin (Prl) or its receptor (PrlR) in humans. Given the essential role of this hormonal system in breast physiology, we reasoned that genetic anomalies of Prl/PrlR genes may be related to the occurrence of breast diseases with high proliferative potential. Multiple fibroadenomas (MFA) are benign breast tumors which appear most frequently in young women, including at puberty, when Prl has well-recognized proliferative actions on the breast. In a prospective study involving 74 MFA patients and 170 control subjects, we identified four patients harboring a heterozygous single nucleotide polymorphism in exon 6 of the PrlR gene, encoding Ile1463 Leu substitution in its extracellular domain. This sole substitution was sufficient to confer constitutive activity to the receptor variant (PrlRI146L), as assessed in three reconstituted cell models (Ba/F3, HEK293 and MCF-7 cells) by Prl-independent (i) PrlR tyrosine phosphorylation, (ii) activation of signal transducer and activator of transcription 5 (STAT5) signaling, (iii) transcriptional activity toward a Prl-responsive reporter gene, and (iv) cell proliferation and protection from cell death. Constitutive activity of PrlRI146L in the breast sample from a patient was supported by increased STAT5 signaling. This is a unique description of a functional mutation of the PrlR associated with a human disease. Hallmarks of constitutive activity were all reversed by a specific PrlR antagonist, which opens potential therapeutic approaches for MFA, or any other disease that could be associated with this mutation in future.antagonist ͉ breast diseases ͉ human mutation ͉ constitutive activity ͉ cytokine receptor

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Section: Discussionmentioning

confidence: 99%

Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors

Bogorad

Courtillot

Mestayer

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Prl induced activation of JAK2 prevents breast cancer cells mesenchymal transition and acts as an invasion suppressor [44,45] . Reduced phosphorylation of STAT5 in breast cancer highlights patients with a worse prognosis of disease development [46] .…”

Section: Jak-stat Signaling and Carcinogenesismentioning

confidence: 99%

JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

Smirnova¹

2007

WJG

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The features of JAK-STAT signaling in liver cells are discussed in the current review. The role of this signaling cascade in carcinogenesis is accentuated. The possible involvement of this pathway and alteration of its elements are compared for normal cholangiocytes, cholangiocarcinoma predisposition and development. Prolactin and interleukin-6 are described in detail as the best studied examples. In addition, the non-classical nuclear translocation of cytokine receptors is discussed in terms of its possible implication to cholangiocarcinoma development.

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“…Wang et al concluded that women whose prolactin level fell postoperatively had significantly shorter overall survival compared with those who had a persistent elevation for 10 days (P \ 0.005). Furthermore, in a recent study, activated Stat5, a key prolactin-induced transcription factor [39], was significantly associated with better prognosis breast cancer [40]. Thus prolactin may have a role in reducing breast cancer incidence [41].…”

Section: Prolactinmentioning

confidence: 93%

Breast-feeding after breast cancer: if you wish, madam

Azim

Bellettini²,

Gelber

et al. 2008

Breast Cancer Res Treat

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Breast cancer is the most common malignant tumor-affecting women during the child bearing period. With the rising trend in delaying pregnancy later in life, the issue of subsequent pregnancy and lactation following breast cancer diagnosis has been more frequently encountered. In this context, data is scarce particularly those addressing the issue of lactation. In this review, we discussed different endocrinal, clinical and biological aspects dealing with breast-feeding after breast cancer in an attempt to determine how safe and feasible this approach is.

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Signal Transducer and Activator of Transcription-5 Activation and Breast Cancer Prognosis

Abstract: In our study, active Stat5 distinguishes breast cancer patients with favorable prognosis, and may be a useful marker for selection of more individualized treatment, especially in localized disease. These findings require confirmation in a large prospective study.

Cited by 208 publications

References 22 publications

Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors

Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors

JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

Breast-feeding after breast cancer: if you wish, madam

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