High-Mobility Group A1 Proteins Regulate p53-Mediated Transcription of <i>Bcl-2</i> Gene

Esposito, Francesco; Tornincasa, Mara; Chieffi, Paolo; Martino, Ivana De; Pierantoni, Giovanna Maria; Fusco, Alfredo

doi:10.1158/0008-5472.can-09-4199

Cited by 55 publications

(53 citation statements)

References 24 publications

(52 reference statements)

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“…HMGA1 overexpression induces inactivation of p53's apoptotic function to escape apoptosis in neoplastic transformation (37,38) and drives stem cell properties in colon cancer cells (39). In our results, HMGA1 expression level was an indicator of poor prognosis in CRC cases and an independent risk factor for lymph node metastasis.…”

Section: Univariate Analysissupporting

confidence: 58%

Microarray analysis reveals that high mobility group A1 is involved in colorectal cancer metastasis

et al. 2013

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Abstract. Tumor size indicates the extent of cell proliferation in most cases of colorectal cancer (CRC), although there are some advanced small tumors with metastases. Lymph node metastasis is a significant factor that greatly impacts disease prognosis in CRC cases. The underlying factors that cause lymph node metastasis in CRC cells are not fully understood. We investigated the mechanism that might induce CRC metastasis by focusing on smaller sized (<2 cm) invasive tumors. We carried out gene expression array analysis for CRC cases; group 1 consisted of 6 cases with tumors <2 cm with metastases, and group 2 consisted of 65 cases with tumors >2 cm without metastases. Results were validated using gene expression array data from an additional 77 cases and another bulk case set of 172 cases. Gene Ontology and pathway analysis using microarray data revealed that anti-apoptotic activity had a crucial role in CRC metastasis. High mobility group A1 (HMGA1) was identified as a biomarker for poor prognosis and metastasis formation. HMGA1 expression levels were higher in lymph node-positive cases than in lymph node-negative cases, even in subgroup analysis of submucosal invasive cases. The present study strongly supports the clinical significance of HMGA1 expression as a predictive indicator of lymph node metastasis in CRC cases, even in submucosal invasive cases which could be cured by local resection.

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Section: Univariate Analysissupporting

confidence: 58%

Microarray analysis reveals that high mobility group A1 is involved in colorectal cancer metastasis

et al. 2013

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“…Protein/DNA binding was determined by EMSA as previously described (46). 5-20 ng of WT and mutant CBX7 recombinant protein (12) was incubated with radiolabeled oligonucleotide (specific activity, 8,000-20,000 cpm/fmol).…”

Section: Methodsmentioning

confidence: 99%

“…Protein extraction, Western blotting, and co-IP procedures were carried out as reported elsewhere (46). The antibodies used were as follows: anti-tubulin (sc-7649; Santa Cruz), anti-p21 (sc-397; Santa Cruz), anti-p19 anti-p16Ink4a (ab-54210; Abcam), anti-cyclin E (sc-481; Santa Cruz), anti-p53 (sc-126; Santa Cruz), anti-phospho-p53 (9284; Cell Signaling), anticyclin A (sc-751; Santa Cruz), anti-CBX7 (a primary antibody raised against the C-terminus of the human CBX7 protein; Neosystem), anti-CBX7 (sc-70232; Santa Cruz), anti-HA (sc-805; Santa Cruz), anti-V5 (Sigma-Aldrich), and anti-HMGA1 (44).…”

Section: Methodsmentioning

confidence: 99%

CBX7 is a tumor suppressor in mice and humans

Forzati¹,

Federico²,

Pallante³

et al. 2012

J. Clin. Invest.

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136

158

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The CBX7 gene encodes a polycomb group protein that is known to be downregulated in many types of human cancers, although the role of this protein in carcinogenesis remains unclear. To shed light on this issue, we generated mice null for Cbx7. Mouse embryonic fibroblasts derived from these mice had a higher growth rate and reduced susceptibility to senescence compared with their WT counterparts. This was associated with upregulated expression of multiple cell cycle components, including cyclin E, which is known to play a key role in lung carcinogenesis in humans. Adult Cbx7-KO mice developed liver and lung adenomas and carcinomas. In in vivo and in vitro experiments, we demonstrated that CBX7 bound to the CCNE1 promoter in a complex that included HDAC2 and negatively regulated CCNE1 expression. Finally, we found that the lack of CBX7 protein expression in human lung carcinomas correlated with CCNE1 overexpression. These data suggest that CBX7 is a tumor suppressor and that its loss plays a key role in the pathogenesis of cancer.

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“…As p53 functions as a tumor suppressor, P53 mutations commonly lead to the development of cancer. By binding p53, HMGA1 interferes with p53-mediated transcription of BAX, P21Waf1, MDM2 and BCL2, leading to a reduction in p53-dependent apoptosis (29)(30)(31). HMGA1 also counteracts p53 transcriptional activity by relocalizing the nuclear p53 proapoptotic activator HIPK2 to the cytoplasm, thereby inhibiting the apoptotic function of p53 (32).…”

Section: A B C Dmentioning

confidence: 99%

“…Recently, HMGA1-p53 interactions have been demonstrated to affect carcinogenesis. HMGA1 binds with p53, thus interfering with the p53-mediated transcription of BCL2-associated X protein (BAX), P21Waf1, MDM2 and B-Cell CLL/Lymphoma 2 (BCL2); this results in reduced p53-dependent apoptosis (29)(30)(31). HMGA1 also inhibits p53 apoptotic function by relocalizing the nuclear p53 proapoptotic activator Homeodomain-interacting protein kinase 2 (HIPK2) to the cytoplasm (32).…”

Section: Introductionmentioning

confidence: 99%

Association of SIRT1 and HMGA1 expression in non-small cell lung cancer

Lin¹,

Peng²

2015

Oncology Letters

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Abstract. The roles of Silent mating type information regulation 2 homolog 1 (SIRT1) and High mobility group A1 (HMGA1) in human diseases have been extensively studied separately; however, to the best of our knowledge, the current study is the first to report on their interrelationship in lung cancer. The association of SIRT1 and HMGA1 in non-small cell lung cancer (NSCLC) was investigated by evaluating their expression and prognostic significance in 260 patients with NSCLC using immunohistochemistry. SIRT1 and HMGA1 expression were found to be significantly correlated with each other (P<0.001), and both were significantly associated with clinicopathological parameters, including histological type and degree of differentiation. In squamous cell carcinoma (SCC), SIRT1 + specimens were significantly associated with shorter overall survival (OS) time (P=0.019). However, in patients with adenocarcinoma (AD), no association was identified between SIRT1 and OS. In addition, HMGA1 + specimens were significantly associated with poor differentiation (P=0.028), and were more frequent in SCC than AD (P=0.015). However, HMGA1 was not associated with OS on univariate Cox regression analysis or Kaplan-Meier analysis (both P>0.05). SIRT1/HMGA1 coexpression was significantly associated with male gender (P=0.016), and moderately and poorly differentiated histological grade (P=0.025). The findings indicate that SIRT1 and HMGA1 may have significant effects during tumor progression in NSCLC, particularly in patients with SCC, and are potentially useful as prognostic indicators for patients with NSCLC.

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High-Mobility Group A1 Proteins Regulate p53-Mediated Transcription of Bcl-2 Gene

Cited by 55 publications

References 24 publications

Microarray analysis reveals that high mobility group A1 is involved in colorectal cancer metastasis

Microarray analysis reveals that high mobility group A1 is involved in colorectal cancer metastasis

CBX7 is a tumor suppressor in mice and humans

Association of SIRT1 and HMGA1 expression in non-small cell lung cancer

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