In vivo evidence of htid suppressive activity on ErbB-2 in breast cancers over expressing the receptor

Kurzik-Dumke, Ursula; Hörner, Manuela; Nicotra, Maria Rita; Koslowski, Michael; Natali, Pier Giorgio

doi:10.1186/1479-5876-8-58

Cited by 6 publications

(6 citation statements)

References 31 publications

(113 reference statements)

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“…We have previously reported that increased expression of Tid1 suppresses the expression level of ErbB2 via the ubiquitin proteasome pathway in human mammary carcinoma cell lines overexpressing ErbB2, and that Tid1 interacts with ErbB2 via its C‐terminus 16. ErbB2/Her‐2/neu transgenic mice revealed that overexpression of ErbB2 correlates with down‐regulation of Tid1 17. Recently, we have also reported that Tid1 attenuates epidermal growth factor receptor (EGFR) signalling by enhancing ubiquitination‐mediated degradation and reduces head and neck squamous cell carcinoma malignancy 18.…”

Section: Introductionmentioning

confidence: 99%

Tid1, CHIP and ErbB2 interactions and their prognostic implications for breast cancer patients

Jan

Hung

et al. 2011

The Journal of Pathology

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ErbB2 (HER2/neu) is overexpressed in about 25-30% of breast malignancies, and up-regulation of ErbB2 in breast cancer patients is associated with poor prognosis. It is known that the carboxyl terminus of heat shock cognate 70 interacting protein (CHIP) efficiently down-regulates ErbB2 in vitro. Human tumourous imaginal disc 1 (Tid1, DnaJa3), a co-chaperone of heat shock protein 70 (Hsp70), also suppresses ErbB2 expression in breast cancer cell lines. However, the intracellular interactions among Tid1, CHIP, and ErbB2 remain elusive, and the utilization of Tid1 and CHIP as breast cancer biomarkers has never been proposed. Herein, we analysed the expression and correlations among Tid1, CHIP, and ErbB2 in a total of 183 breast cancer histology sections, including 30 fresh tissue specimens, using immunohistochemistry (IHC) and immunoblotting assay. A computerized image analysis system was used for IHC scoring and determining relative immunoblot intensity. The immunohistochemical expression of Tid1 and CHIP were positively correlated with each other but were both inversely correlated to that of ErbB2. Odds ratio analyses showed that lower expression of Tid1 has a relatively higher risk of unfavourable tumour grade, later pathological stage, larger tumour size, and microscopic features of a more malignant histology including lymphovascular invasion, stromal inflammatory response, and tumour necrosis. Expression of CHIP displayed similar characteristics. Furthermore, expression of Tid1 and/or CHIP increases patients' 10-year overall and disease-free survival rate. Empirically, we also demonstrated that Tid1, CHIP, and ErbB2 interacted with each other through immunofluorescence or co-immunoprecipitation analyses. Functionally, Tid1 and CHIP acted synergistically to degrade ErbB2 in vitro. Conversely, Tid1 cannot compensate for the loss of proteolytic function noted in CHIP mutations for degradation of ErbB2. Overall, our data suggest that Tid1 and CHIP play pivotal roles in affecting the levels of ErbB2 protein, and that both are significant prognostic indicators of breast cancer patient survival.

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Section: Introductionmentioning

confidence: 99%

Tid1, CHIP and ErbB2 interactions and their prognostic implications for breast cancer patients

Jan

Hung

et al. 2011

The Journal of Pathology

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“…Loss of Tid1 expression has been shown to be associated with human basal cell carcinoma but not with normal keratinocytes 20 . Overexpression of Tid1 reduces the tumorigenicity of breast cancer cells in nude mice and reduces anchorage-independent growth in lung adenocarcinoma cell lines 21 , 22 . Similarly, in our present study ISO treatment decreased Tid1 expression; however, Tid1S overexpression blocked the ISO-induced calcineurin/NFATc3 hypertrophy pathway, reduced the apoptotic effects and increased H9c2 cell survival.…”

Section: Discussionmentioning

confidence: 99%

Tumorous imaginal disc 1 (TID1) inhibits isoproterenol-induced cardiac hypertrophy and apoptosis by regulating c-terminus of hsc70-interacting protein (CHIP) mediated degradation of Gαs

et al. 2018

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Dilated cardiomyopathy (DCM) is the most common form of non-ischemic cardiomyopathy. It is characterized by ventricular chamber dilation, and myocyte hypertrophy. Human tumorous imaginal disc 1 (Tid1), a chaperone protein and response to regulate number of signaling molecules in the mitochondria or cytosol. Tid1 also plays a major role in preventing DCM; however, the role of Tid1 in isoproterenol (ISO)-induced cardiac apoptosis and hypertrophy remains unclear. H9c2 cells were pretreated Tid1 before ISO-induced hypertrophy and apoptosis and then evaluated by IHC, TUNEL assay, IFC, Co-IP, and Western blot. From the IHC experiment, we found that Tid1 proteins were increased in tissues from different stages of human myocardial infarction. Using H9c2 cardiomyoblast cells we found that Tid1 was decreased by ISO treatment. However, over-expression of Tid1S suppressed NFATc3, BNP and calcineurin protein expression and inhibited NFATc3 nuclear translocation in ISO induced cardiomyoblast cells. On the other hand, Tid1S over-expression activated survival proteins p-AKTser473 and decreased caspase-3 and cytochrome c expression. We also found that overexpression of Tid1 enhanced CHIP expression, and induced CHIP to ubiquitinate Gαs, resulting in increased Gαs degradation. Our study showed that Gαs is a novel substrate of CHIP, and we also found that the Tid1-CHIP complex plays an essential role in inhibiting ISO induced cardiomyoblast hypertrophy and apoptosis.

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“…Finally, increased cellular DNAJA3 inhibited the growth of ErbB-2-dependent tumors in mice (Kim et al, 2004). Mammary tumor tissue from breast cancer patients and transgenic mice carrying the rat HER-2/neu oncogene suggest that DNAJA3 suppresses ErbB-2 in breast cancers (Kurzik-Dumke et al, 2010). NF-kappaB: expression of DNAJA3 was upregulated upon cellular senescence in rat and mouse embryo fibroblasts, as well as in premature senescence of REF52 cells triggered by activated ras.…”

Section: Mitochondrial Functionsmentioning

confidence: 97%

“…Aberrant expression of all three forms correlated with malignant transformation. Furthermore, elevated DNAJA3L expression was associated with less aggressive tumors (Kurzik-Dumke et al, 2010). Immunohistochemical analysis demonstrated high levels of DNAJA3 protein in tumors of the luminal A subtype, but significantly lower levels of DNAJA3 protein in the luminal B subtype, triple negative tumors, and the HER-2 subtype which overexpresses HER-2 (Kurzik-Dumke et al, 2010).…”

Section: Breast Cancermentioning

confidence: 99%

DNAJA3 (DnaJ (Hsp40) homolog, subfamily A, member 3)

Traicoff¹,

Hewitt²,

Chung³

2012

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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In vivo evidence of htid suppressive activity on ErbB-2 in breast cancers over expressing the receptor

Cited by 6 publications

References 31 publications

Tid1, CHIP and ErbB2 interactions and their prognostic implications for breast cancer patients

Tid1, CHIP and ErbB2 interactions and their prognostic implications for breast cancer patients

Tumorous imaginal disc 1 (TID1) inhibits isoproterenol-induced cardiac hypertrophy and apoptosis by regulating c-terminus of hsc70-interacting protein (CHIP) mediated degradation of Gαs

DNAJA3 (DnaJ (Hsp40) homolog, subfamily A, member 3)

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