Possible role of Stat5a in rat mammary gland carcinogenesis

Shan, Liang; Yu, Minshu; Clark, Bradly; Snyderwine, Elizabeth G.

doi:10.1007/s10549-004-0805-2

Cited by 27 publications

(26 citation statements)

References 25 publications

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“…This has been reported in one study where 76% of the breast cancers examined showed phosphorylated STAT 5a to be present in the nucleus [8]. It has also been shown that in 65% of induced rat mammary gland tumors, STAT 5a was detected in the nucleus using phosphorylation-specific antibodies [23].…”

Section: Discussionmentioning

confidence: 60%

STAT 5a expression in various lesions of the breast

2005

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The seven signal transducer and activator of transcription (STAT) molecules are effectors of hormonal or cytokine stimulation through receptors. STAT 5a, isolated from prolactin-stimulated mammary cells, contributes to normal proliferation and is essential for mammary gland differentiation. Using a monoclonal antibody, we tested 100 formalin-fixed, paraffin-embedded breast tissues representing everything from simple hyperplasia to invasive carcinoma for the expression of STAT 5a in comparison to normal breast epithelial cells. Immunohistochemical analysis was performed following heat treatment in a pressure cooker. STAT 5a was found in endothelial cells, adipocytes, and leukocytes as well as in the cytoplasm and nucleus of normal epithelial cells, usual ductal hyperplasia, and benign lesions such as fibroadenoma. Myoepithelial cells and stromal fibroblasts failed to demonstrate any STAT 5a in addition to most atypical proliferations including in situ and invasive carcinomas. A few examples of lobular intraepithelial neoplasia and invasive carcinoma demonstrated some reactivity, albeit comparatively reduced. The absence of STAT 5a in the abnormal breast epithelial cells may indicate a defect contributory to the abnormal state.

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Section: Discussionmentioning

confidence: 60%

STAT 5a expression in various lesions of the breast

2005

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“…In the same study, a significant correlation between a high STAT5A nuclear expression and high tumour grade was observed. A significantly increased nuclear localisation of STAT5A has also been shown in human BCs (Cotarla et al 2004, Shan et al 2004.…”

Section: Introductionmentioning

confidence: 67%

“…Immunohistochemical approaches in humans have found increased levels of nuclear localised STAT3 in malignant BCs when compared with normal tissues (Clevenger 2004). Nuclear expression of STAT5A in chemically induced rat mammary gland cancers and preneoplastic lesions has been detected, when compared with cytosolic STAT5A expression in the control tissue (Shan et al 2004). In the same study, a significant correlation between a high STAT5A nuclear expression and high tumour grade was observed.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the Janus kinase 2 (JAK)/signal transducer and activator of transcription (STAT) genes: putative association of the STAT gene region with familial breast cancer

Vaclavicek¹,

Bermejo²,

Schmutzler³

et al. 2007

Endocr Relat Cancer

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The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway mediates the signals of a wide range of cytokines, growth factors and hormones. Thus, aberrant activation of the JAK/STAT pathway may predispose to malignancy due to deregulation of proliferation, differentiation or apoptosis. In this study, we investigated whether genetic variation in the JAK2 gene and the STAT gene region (STAT3, STAT5A and STAT5B) is associated with breast cancer (BC) risk. We carried out a case-control study using a German sample set with 441 familial, unrelated BC cases and 552 controls matched by age, ethnicity and geographical region. A second similar set (381 cases, 460 controls) was applied to validate the findings. Haplotypes in the JAK2 gene were not associated with the risk of BC. In the STAT gene region, the rare haplotype CAGCC containing the variant alleles of each single nucleotide polymorphism (SNP) was associated with an increased risk odds ratio (ORZ5.83, 95% confidence interval (CI) 1.51-26.28). According to Akaike's information criterion, the best model to describe the relationship between the haplotypes and BC was based on the SNPs rs6503691 (STAT5B) and rs7211777 (STAT3). Carriers of the AC haplotype, which represents the variant alleles of both SNPs, were at an increased risk (ORZ1.41, 95% CI 1.09-1.82). A decreased risk was observed for carriers of the AT haplotype (ORZ0.60, 95% CI 0.38-0.94). Furthermore, individuals with the AC/GC diplotype were at a significantly increased risk (ORZ1.88, 95% CI 1.13-3.14). The observed genetic variation may also influence the inter-individual variation in response to STAT-signalling targeted therapy.

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“…In a study using the rat mammary gland as a model, Shan et al (2004) examined the immunohistochemical expression and activation of STAT5A in a panel of rat mammary gland carcinomas induced by the chemical carcinogens, 7,12-dimethylbenz[a]anthracene and 2-amino-1-methyl-6 phenylimidazo [4,5-b]pyridine, to assess the percentage of cells in carcinomas and preneoplastic lesions showing tyrosine phosphorylated and nuclear localized STAT5A. Nuclear immunostaining of STAT5A was detected in 65% of carcinomas, while STAT5A in control normal mammary gland tissue was cytosolic.…”

Section: Stat5a/b In Tumorigenesis Of Rodent Mammary Glandmentioning

confidence: 99%

Signal transducer and activator of transcription 5A/B in prostate and breast cancers

Tan

Nevalainen

2008

Endocrine Related Cancer

100

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Protein kinase signaling pathways, such as Janus kinase 2-Signal transducer and activator of transcription 5A/B (JAK2-STAT5A/B), are of significant interest in the search for new therapeutic strategies in both breast and prostate cancers. In prostate cancer, the components of the JAK2-STAT5A/B signaling pathway provide molecular targets for small-molecule inhibition of survival and growth signals of the cells. At the same time, new evidence suggests that the STAT5A/B signaling pathway is involved in the transition of organ-confined prostate cancer to hormonerefractory disease. This implies that the active JAK2-STAT5A/B signaling pathway potentially provides the means for pharmacological intervention of clinical prostate cancer progression. In addition, active STAT5A/B may serve as a prognostic marker for identification of those primary prostate cancers that are likely to progress to aggressive disease. In breast cancer, the role of STAT5A/B is more complex. STAT5A/B may have a dual role in the regulation of malignant mammary epithelium. Data accumulated from mouse models of breast cancer suggest that in early stages of breast cancer STAT5A/B may promote malignant transformation and enhance growth of the tumor. This is in contrast to established breast cancer, where STAT5A/B may mediate the critical cues for maintaining the differentiation of mammary epithelium. In addition, present data suggest that activation of STAT5A/B in breast cancer predicts favorable clinical outcome. The dual nature of STAT5A/B action in breast cancer makes the therapeutic use of STAT5 A/B more complex.

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Possible role of Stat5a in rat mammary gland carcinogenesis

Cited by 27 publications

References 25 publications

STAT 5a expression in various lesions of the breast

STAT 5a expression in various lesions of the breast

Polymorphisms in the Janus kinase 2 (JAK)/signal transducer and activator of transcription (STAT) genes: putative association of the STAT gene region with familial breast cancer

Signal transducer and activator of transcription 5A/B in prostate and breast cancers

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