Misexpression of Wild-Type and Truncated Isoforms of the High-Mobility Group I Proteins HMGI-C and HMGI(Y) in Uterine Leiomyomas

Klotzbücher, Michael; Wasserfall, Annemarie; Fuhrmann, Ulrike

doi:10.1016/s0002-9440(10)65469-7

Cited by 50 publications

(29 citation statements)

References 32 publications

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“…The finding was also supported from another study. 6 Our data of expression of high mobility group protein A2 in a relative large sampling (60 cases) are compatible with results mentioned above.…”

Section: Discussionsupporting

confidence: 91%

“…They bind in the minor groove of DNA and it has been suggested to be a transcription factor. 6,38,39 The causal relation between changes in these high mobility group protein genes and aberrant growth control in benign tumors remains to be established. 3 Tallini et al 5 found that about 36% (9/25) of leiomyomata presented chromosomal alteration involving chromosome 12, near high-mobility group protein gene A2 locus.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 In our study, we examined highmobility group protein gene A2 in terms of its association with other proteins. Differential expression of high-mobility group protein gene A2 was noted in 26 out of 56 cases (46.4%).…”

Section: Immunohistochemical Data In the Panelsmentioning

confidence: 99%

“…3,4 The high-mobility group protein genes are considered candidate genes for leiomyomata as these were identified from breakpoints of chromosomal translocation in leiomyomata. 3,5 Although an upregulation of high-mobility group protein gene A2 has been found in some leiomyomata, 5,6 the fusion highmobility group protein gene A2 by truncated transcripts at translocation breakpoints is not a common molecular event. 7 Gene chip studies have provided a means of identifying differentially expressed genes in leiomyomata.…”

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confidence: 99%

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Expression profile of tuberin and some potential tumorigenic factors in 60 patients with uterine leiomyomata

et al. 2005

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Human uterine leiomyomata are the most common tumors in women of reproductive age. The pathogenesis of leiomyomata remains unknown. An animal model of Eker rats with deleted tuberous sclerosis complex gene 2 (tuberin) shows increased incidence of leiomyomata. The role of tuberin in human leiomyomata is unknown. In this study, we designed a tissue microarray with tissue cores of leiomyomata and the matched myometrium from 60 hysterectomy specimens. We examined the expression of tuberin and tuberous sclerosis complex gene 1 product hamartin, proteins of the insulin-signaling pathway, steroid receptors and some of their cofactors, and human mobility group gene A2 by immunohistochemistry. We found that nearly half of the cases displayed either reduction or loss of tuberin in leiomyomata compared with matched normal myometrium. No change of hamartin was noted. Furthermore, a significant reduction of glucocorticoid receptor was found in leiomyomata with reduced tuberin. The proteins insulin like growth factor 1, insulin-like growth factor receptor b, AKT kinase, and phosphatidylinositol 3-kinase were upregulated. Nearly half of leiomyomata show upregulation of human mobility group gene A2, along with the steroid receptor cofactors. Our findings suggest that there are two broad groups of uterine leiomyomata. One group is associated with an alteration of tuberin and glucocorticoid receptor. The other group is associated with upregulation of human mobility group gene A2 and steroid receptor cofactors.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Immunohistochemical Data In the Panelsmentioning

confidence: 99%

mentioning

confidence: 99%

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Expression profile of tuberin and some potential tumorigenic factors in 60 patients with uterine leiomyomata

et al. 2005

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“…These findings and studies on HMGI-C expression in a variety of tumours (Chiappetta et al, 1995;Kazmierczak et al, 1996Kazmierczak et al, , 1998Staats et al, 1996;Rogalla et al, 1997Rogalla et al, , 1998Rommel et al, 1997;Giannini et al, 1999;Klotzbucher et al, 1999) have substantiated the important role of HMGI-C in the control of cell growth, differentiation and tumorigenesis. It could also be detected in the peripheral blood of patients with leukaemia, but no HMGI-C expression could be found in the peripheral blood samples of healthy donors (Rommel et al, 1997;Sezer et al, 2000).…”

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confidence: 67%

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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Surgical treatment of fibroids for subfertility

Griffiths¹,

D’Angelo²,

Amso³

2002

The Cochrane Database of Systematic Reviews

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Misexpression of Wild-Type and Truncated Isoforms of the High-Mobility Group I Proteins HMGI-C and HMGI(Y) in Uterine Leiomyomas

Cited by 50 publications

References 32 publications

Expression profile of tuberin and some potential tumorigenic factors in 60 patients with uterine leiomyomata

Expression profile of tuberin and some potential tumorigenic factors in 60 patients with uterine leiomyomata

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

Surgical treatment of fibroids for subfertility

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