Differential PIAS3 expression in human malignancy

Wang, Liming; Banerjee, Sipra

doi:10.3892/or.11.6.1319

Cited by 83 publications

(94 citation statements)

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“…Again, these findings are concordant with a previous study examining tumors throughout the body (including breast) that noted increased PIAS3 expression as a function of malignant transformation. 35 Data from the current study also demonstrates a strong correlation between visual scoring of breast tissue microarrays by two independent observers and quantitative image analysis using the ACIS system. In the ACIS analysis no attempt was made to segregate regions of interest.…”

Section: Signaling In Breast Cancer K Mchale Et Alsupporting

confidence: 60%

Altered expression of prolactin receptor-associated signaling proteins in human breast carcinoma

et al. 2008

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Prolactin receptor signaling can modulate proliferation, survival, motility, angiogenesis, and differentiation in breast cancer. Increased serum prolactin is associated with a significantly increased risk of breast cancer in post-menopausal women. The purpose of this study was to examine the expression of prolactin receptorassociated signaling proteins in breast cancer vs benign breast tissue. Breast tissue microarrays representing 40 cases of benign and malignant pathologies were obtained from the Cooperative Human Tissue Network. Standard immunohistochemistry for prolactin and prolactin receptor-associated proteins was performed. Both positive regulators (c-Myb, Nek3, Vav2) and negative regulators (PIAS3, SIRP) of prolactin receptor signaling were examined. Virtual slides were created from the stained breast tissue microarrays. Labels were scored by region of interest and labeling indices incorporating percent target labeled and label intensity were created. Quantitative determinations of labels were made using the Clarient image system. The unpaired t-test was used to compare labels from benign and malignant tissues. Visual scoring data showed upregulation of Nek3 (P ¼ 0.000377), PIAS3 (P ¼ 0.000257), and prolactin (P ¼ 0.002576) in breast cancer vs normal/hyperplastic epithelium. c-Myb showed a trend toward upregulation, but this did not achieve statistical significance (P ¼ 0.107374). SIRP (P ¼ 0.002060) was downregulated. Vav2 showed a trend toward downregulation (P ¼ 0.107456), but this did not achieve statistical significance. Clarient analysis corroborated upregulation in cancer of Nek3 (P ¼ 0.000013), PIAS3 (P ¼ 0.000067), and prolactin (P ¼ 0.017569). In conclusion, regulators of prolactin receptor signaling show heterogeneity in their expression in benign vs malignant breast tissue. Since these species are known to regulate prolactin-mediated actions, these results suggest multiple targets for modulating prolactin receptor-mediated growth and differentiation in breast cancer. The neuroendocrine hormone prolactin contributes to breast cancer progression through both endocrine and autocrine/paracrine loops. Prolactin acts through its cell-surface receptor, the prolactin receptor, and triggers a network of prolactin receptor-associated signaling proteins. In normal tissues, prolactin stimulates lobulo-alveolar expansion and differentiation as a prelude to milk synthesis and secretion. 1 In malignant tissues, however, prolactin fails to trigger differentiation, and instead enhances breast epithelial survival and motility. [2][3][4] Both normal and malignant breast epithelia, besides responding to pituitary-secreted (endocrine) prolactin, synthesize prolactin RNA from an upstream promoter at the autocrine/paracrine level. 4 As mutations of the prolactin receptor are very infrequent in breast cancer, we hypothesized that dysregulation of local prolactin production or prolactin receptor-associated signaling machinery may contribute to some of the altered actions of prolactin in this disease.This study focus...

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Section: Signaling In Breast Cancer K Mchale Et Alsupporting

confidence: 60%

Altered expression of prolactin receptor-associated signaling proteins in human breast carcinoma

et al. 2008

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“…The hinge region of ERα is a specific target of SUMO-E3 ligases (catalyzes the covalent attachment of a SUMO), Protein inhibitor of Activated STAT (PIAS1), and PIAS3 [149]. An increase in expression of PIAS3 has been documented in breast cancer [150]. Proteomics also identified K299 in the hinge region and K472 in the steroid-binding domain to be sumoylated.…”

Section: Sumoylation Of Estrogen Receptormentioning

confidence: 99%

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

Zhou

Qiao

Shetty

et al. 2013

Cell. Mol. Life Sci.

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Estrogen and estrogen receptors (ERs) are critical regulators of breast epithelial cell proliferation, differentiation, and apoptosis. Compromised signaling vis-à-vis the estrogen receptor is believed © Springer Basel 2013 yow4@pitt.edu. ), which predicts for response to endocrine-based therapy; however, innate or acquired resistance to endocrinebased drugs remains a serious challenge. The complexity of regulation for estrogen signaling coupled with the crosstalk of other oncogenic signaling pathways is a reason for endocrine therapy resistance. Alternative strategies that target novel molecular mechanisms are necessary to overcome this current and urgent gap in therapy. A thorough analysis of estrogen-signaling regulation is critical. In this review article, we will summarize current insights into the regulation of estrogen signaling as related to breast carcinogenesis and breast cancer therapy. NIH Public Access

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“…In addition, we found a band of higher molecular weight in spleen and lung extracts. This band represents the 85-kDa sumoylated form of PIAS3 (25,26). Interestingly, the expression of PIAS3 largely corresponds to the activation pattern STAT3 in the same tissues.…”

Section: Pias3 Is Differentially Expressed In Normal Mouse Tissuesmentioning

confidence: 99%

“…Northern blot analysis, reverse transcription-PCR analysis, and immunohistochemical analyses have been done (7,(24)(25). We extended these studies and carried out Western blot analyses of freshly prepared mouse tissue protein extracts.…”

Section: Pias3 Is Differentially Expressed In Normal Mouse Tissuesmentioning

confidence: 99%

The Intracellular Delivery of a Recombinant Peptide Derived from the Acidic Domain of PIAS3 Inhibits STAT3 Transactivation and Induces Tumor Cell Death

Borghouts

Tittmann

Delis

et al. 2010

Molecular Cancer Research

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Signaling components, which confer an "addiction" phenotype on cancer cells, represent promising drug targets. The transcription factor signal transducers and activators of transcription 3 (STAT3) is constitutively activated in many different types of tumor cells and its activity is indispensible in a large fraction. We found that the expression of the endogenous inhibitor of STAT3, protein inhibitor of activated STAT3 (PIAS3), positively correlates with STAT3 activation in normal cells. This suggests that PIAS3 controls the extent and the duration of STAT3 activity in normal cells and thus prevents its oncogenic function. In cancer cells, however, the expression of PIAS3 is posttranscriptionally suppressed, possibly enhancing the oncogenic effects of activated STAT3. We delimited the interacting domains of STAT3 and PIAS3 and identified a short fragment of the COOH-terminal acidic region of PIAS3, which binds strongly to the coiled-coil domain of STAT3. This PIAS3 fragment was used to derive the recombinant STAT3-specific inhibitor rPP-C8. The addition of a protein transduction domain allowed the efficient internalization of rPP-C8 into cancer cells. This resulted in the suppression of STAT3 target gene expression, in the inhibition of migration and proliferation, and in the induction of apoptosis at low concentrations [half maximal effective concentration (EC 50 ), <3 μmol/L]. rPP-C8 did not affect normal fibroblasts and represents an interesting lead for the development of novel cancer drugs targeting the coiled-coil domain of STAT3. Mol Cancer Res; 8(4); 539-53. ©2010 AACR.

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Differential PIAS3 expression in human malignancy

Cited by 83 publications

References 0 publications

Altered expression of prolactin receptor-associated signaling proteins in human breast carcinoma

Altered expression of prolactin receptor-associated signaling proteins in human breast carcinoma

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

The Intracellular Delivery of a Recombinant Peptide Derived from the Acidic Domain of PIAS3 Inhibits STAT3 Transactivation and Induces Tumor Cell Death

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