A retrospective study of high mobility group protein I(Y) as progression marker for prostate cancer determined by in situ hybridization

Tamimi, Yahya; Poel, H.G. Van Der; Karthaus, H. F. M.; Debruyne, F. M. J.; Schalken, Jack A.

doi:10.1038/bjc.1996.403

Cited by 110 publications

(126 citation statements)

References 31 publications

(17 reference statements)

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“…Indeed, increased HMGA levels correlate with the appearance of a malignant phenotype in rat thyroid cells and in experimental thyroid and skin tumours. [7][8][9] HMGA1 levels are high in human thyroid, 10,11 colon, [12][13][14] prostate, 15 pancreas, 16 cervix, 17 ovary 18 and breast 19 carcinomas. We had previously demonstrated that overexpression of HMGA proteins is required for cell transformation, since the blockage of their synthesis prevents tumorigenic transformation of rat thyroid cells by murine transforming retroviruses.…”

Section: Introductionmentioning

confidence: 99%

High Mobility Group A1 (HMGA1) proteins interact with p53 and inhibit its apoptotic activity

et al. 2005

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HMGA gene overexpression and rearrangements are frequent in several tumours, but their oncogenic function is still unclear. Here we report of a physical and functional interaction between High Mobility Group A1 (HMGA1) protein and p53 oncosuppressor. We found that HMGA1 binds p53 in vitro and in vivo, and both proteins are present in the same complexes bound to the Bax gene promoter. HMGA1 interferes with the p53-mediated transcription of p53 effectors Bax and p21 waf1 while cooperates with p53 in the transcriptional activation of the p53 inhibitor mdm2. This transcriptional modulation is associated with a reduced p53-dependent apoptosis in cells expressing exogenous HMGA1 and p53, or in cells expressing endogenously the proteins and in which p53 was activated by UV-irradiation. Furthermore, antisense inhibition of HMGA1b expression dramatically increases the UV-induced p53-mediated apoptosis. These data define a new physical and functional interaction between HMGA1 and p53 that modulates transcription of p53 target genes and inhibits apoptosis.

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Section: Introductionmentioning

confidence: 99%

High Mobility Group A1 (HMGA1) proteins interact with p53 and inhibit its apoptotic activity

et al. 2005

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“…In a study on colorectal neoplastic tissues a correlation could be found between an increased HMGI(Y) protein expression because of an increase in its mRNA and various clinicopathological parameters, known to be HMGI-C mRNA expression in metastatic breast cancer C Langelotz et al indicative of a poor prognosis (Abe et al, 1999). A significant correlation between HMGI(Y) mRNA expression and tumour grade and stage could be found in another study on prostate cancer (Tamimi et al, 1996). The above data demonstrate that HMGI-C and HMGI(Y) are important elements in tumorigenesis, while a precise definition of their role in tumour initiation and progression is still missing.…”

Section: Discussionmentioning

confidence: 60%

Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer

et al. 2003

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HMGI-C belongs to the high-mobility-group-protein (HMG) family of architectural transcription factors and considerable interest has recently been shown in its expression in neoplastic tissues and apparent involvement in tumorigenesis. We could previously demonstrate an expression of HMGI-C mRNA in the peripheral blood of breast cancer patients for the first time. In this prospective study, we evaluated the independent prognostic power of HMGI-C mRNA expression in the peripheral blood of an unselected cohort of 69 patients with metastatic breast cancer using a hemi-nested reverse transcriptase polymerase chain reaction (RT -PCR) followed by sequence analysis of the resulting PCR products. Multivariate analysis was performed using the Cox regression model. HMGI-C mRNA was detected in peripheral blood from 21 out of 69 (30%) patients with metastatic breast cancer. Median survival was 15.9 months in patients expressing HMGI-C, while in the group of patients without HMGI-C expression the median survival had not been reached yet after a median follow-up of 24.7 months and 85.4% were still alive in this group. Disease-specific survival was significantly worse for patients positive for HMGI-C in comparison to those not expressing HMGI-C (P ¼ 0.0001). In a multivariate regression analysis, HMGI-C remained an independent prognostic factor for overall survival (P ¼ 0.001) besides oestrogen receptor status (P ¼ 0.024) and presence of metastases in liver and lungs (P ¼ 0.029). HMGI-C expression in the peripheral blood of patients with metastatic breast cancer is a powerful independent indicator for poor overall survival and this is the first study to demonstrate its prognostic relevance in univariate and multivariate analysis.

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“…During embryogenesis, HMGA protein expression is high (15,16), whilst normal adult tissues exhibit low or undetectable HMGA expression. However, high HMGA expression levels have been observed in human malignant neoplasias, including carcinomas of the thyroid (17), colon (18), prostate (19), pancreas (20), cervix (21), ovary (22) and breast (23). Although HMGA proteins alone do not exert transcriptional activity, they are able to alter chromatin structure, and thus regulate the expression of a number of genes, by interacting with the transcription machinery (24,25).…”

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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A retrospective study of high mobility group protein I(Y) as progression marker for prostate cancer determined by in situ hybridization

Abstract: Summary In a previous study using RNA in

Cited by 110 publications

References 31 publications

High Mobility Group A1 (HMGA1) proteins interact with p53 and inhibit its apoptotic activity

High Mobility Group A1 (HMGA1) proteins interact with p53 and inhibit its apoptotic activity

Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer

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

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