Identification of a YAC spanning the translocation breakpoints in uterine leiomyomata, pulmonary chondroid hamartoma, and lipoma: physical mapping of the 12q14–q15 breakpoint region in uterine leiomyomata

Fejzo, Marlena S.; Yoon, Sangmoon; Montgomery, Kate; Rein, Mitchell S.; Weremowicz, Stanislawa; Krauter, Kenneth; Dorman, Thomas E.; Fletcher, Jonathan A.; Mao, Jen-i; Moir, Donald T.; Kucherlapati, Raju

doi:10.1016/0888-7543(95)80210-d

Cited by 45 publications

(10 citation statements)

References 27 publications

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“…Evidence of its role in the development of a variety of benign tumors, mostly of mesenchymal origin, including lipomas, uterine leiomyomas, fibroadenomas of the breast, aggressive angiomyxomas, endometrial polyps and pulmonary hamartomas has been provided by cytogenetic studies (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Although the HMGA2 gene is probably one of the most commonly rearranged genes in human neoplasms its precise function in the development and progression of tumors is still unknown (6,10,13,14). Originally, HMGA2 was discovered as an acid-soluble nuclear protein that was expressed at high levels following transformation of fibroblasts and thyroid cells in oncogenic viruses and during embryonic development (2).…”

Section: Introductionmentioning

confidence: 99%

HMGA2 is associated with invasiveness but not a suitable marker for the detection of circulating tumor cells in breast cancer

Fabjani

Tong²,

Wolf³

et al. 2005

Oncol Rep

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Previously, the human high mobility group protein member HMGA2 mRNA was reported to be expressed in peripheral blood of patients with breast cancer, but not in healthy individuals. Expression of HMGA2 in blood was suggested to be an independent indicator of poor prognosis in metastatic breast cancer. These very promising findings propose HMGA2 as a potential marker for the detection of circulating tumor cells in peripheral blood. Therefore, we analyzed peripheral blood specimens from healthy controls and patients with breast tumors for HMGA2 expression using TaqMan ® real-time RT-PCR to test if HMGA2 is a suitable marker for the early detection of breast cancer and monitoring therapy response in peripheral blood. Furthermore, we examined the possible involvement of HMGA2 expression in invasion investigated by an in vitro invasion assay using established breast cell lines. HMGA2 expression was detected in peripheral blood of breast cancer patients as well as of healthy individuals. No significant association of HMGA2 expression with any clinical or histopathological data was apparent. However, there was a significant correlation of HMGA2 expression in invasive and non invasive breast cell lines (p=0.0056). Although, HMGA2 obviously contributes to invasion it is not a specific marker for the detection of circulating tumor cells in peripheral blood.

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Section: Introductionmentioning

confidence: 99%

HMGA2 is associated with invasiveness but not a suitable marker for the detection of circulating tumor cells in breast cancer

Fabjani

Tong²,

Wolf³

et al. 2005

Oncol Rep

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“…Our finding that cyclin A is a direct target gene of HMGA2 is consistent with the role proposed for HMGA2 in cell transformation and cell growth during embryogenesis. The HMGA2 protein has been implicated in the pathogenesis of a variety of benign solid human tumors (2,20,47,50), and its role has been demonstrated by using transgenic mice overexpressing wild-type HMGA2 or HMGA2 mutants (1,3,6,18,19). Moreover, it was reported that the pygmy phenotype in mice was caused by the disruption of both Hmga2 alleles (55).…”

Section: E4fmentioning

confidence: 99%

“…In addition, chromatin immunoprecipitation experiments show that HMGA2 associates with the cyclin A promoter only when the gene is transcriptionally activated. These data identify the cyclin A gene as a cellular target for HMGA2 and, for the first time, suggest a mechanism for HMGA2-dependent cell cycle regulation.HMGA2 belongs, together with HMGA1a and HMGA1b, to the HMGA family of nuclear proteins, whose expression has functional implications in the pathogenesis of several human tumors (2,20,47,50). A strong association between the expression of these proteins and the transformed phenotype has been observed since they were first described, in transformed rat thyroid cells (24,25), and was later found in several human neoplasias (e.g., colon, prostate, cervical, and thyroid carcinomas) (4, 10, 17, 51).…”

mentioning

confidence: 99%

Transcriptional Activation of the Cyclin A Gene by the Architectural Transcription Factor HMGA2

Tessari¹,

Gostissa

Altamura³

et al. 2003

Molecular and Cellular Biology

127

108

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The HMGA2 protein belongs to the HMGA family of architectural transcription factors, which play an important role in chromatin organization. HMGA proteins are overexpressed in several experimental and human tumors and have been implicated in the process of neoplastic transformation. Hmga2 knockout results in the pygmy phenotype in mice and in a decreased growth rate of embryonic fibroblasts, thus indicating a role for HMGA2 in cell proliferation. Here we show that HMGA2 associates with the E1A-regulated transcriptional repressor p120 E4F , interfering with p120 E4F binding to the cyclin A promoter. Ectopic expression of HMGA2 results in the activation of the cyclin A promoter and induction of the endogenous cyclin A gene. In addition, chromatin immunoprecipitation experiments show that HMGA2 associates with the cyclin A promoter only when the gene is transcriptionally activated. These data identify the cyclin A gene as a cellular target for HMGA2 and, for the first time, suggest a mechanism for HMGA2-dependent cell cycle regulation.HMGA2 belongs, together with HMGA1a and HMGA1b, to the HMGA family of nuclear proteins, whose expression has functional implications in the pathogenesis of several human tumors (2,20,47,50). A strong association between the expression of these proteins and the transformed phenotype has been observed since they were first described, in transformed rat thyroid cells (24,25), and was later found in several human neoplasias (e.g., colon, prostate, cervical, and thyroid carcinomas) (4, 10, 17, 51). Their expression is very low, if not absent, in adult tissues and is restricted to embryogenesis (11,28,32,55).The first evidence of a direct role played by these factors in tumorigenesis came from transfection of an antisense construct for HMGA2 in normal rat thyroid cells that prevented the neoplastic transformation induced by myeloproliferative sarcoma virus and kirsten murine sarcoma virus (7). More recently, the increased expression of all three HMGA family members was shown to lead to transformation with anchorageindependent cell growth (53, 54), and the overexpression of HMGA1 was also shown to promote tumor progression in human breast epithelial cells (41). Of additional interest, rearrangements of the HMGA2 gene, resulting in the loss of the acidic C-terminal tail, have been frequently detected in benign human tumors of mesenchimal origin (50). Indeed, transgenic mice expressing the truncated HMGA2 protein develop tumors such as lipomas and natural killer lymphomas (1, 3, 6, 18), while mice expressing wild-type HMGA2 develop pituitary adenomas (19).Despite this evidence, the molecular events and the precise role played by HMGA2 in cell proliferation and tumorigenesis still need to be defined.HMGA proteins contain about 100 amino acid residues and have three DNA-binding domains which have been named AT hooks because of their ability to interact with the narrow minor groove of AT-rich DNA sequences (42). These nuclear proteins, by binding to DNA and/or to transcription factors, can organi...

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“…The incidence rate of diagnosed uterine leiomyoma was 12.8 per 1000/year women in one prospective cohort of women aged 25-44 (1) , and leiomyoma are the most commonly listed discharge diagnoses for hysterectomy in the United States (2) . Despite the clinical and public health importance of uterine leiomyoma, no certain drug treatment except surgery and no prevention method give us significant limitations for the management of these tumors.Multiple genetic approaches revealed that uterine leiomyomas are clonal tumors (3) as well as the steroid and growth factors dependency and uterine leiomyoma have the characteristic chromosomal rearrangement, such as a del(7q) and a t(12;14) rearrangement (4,5) . Previous studies suggested that two possible pathways are involved in the proliferation of uterine leiomyoma.…”

mentioning

confidence: 99%

“…Multiple genetic approaches revealed that uterine leiomyomas are clonal tumors (3) as well as the steroid and growth factors dependency and uterine leiomyoma have the characteristic chromosomal rearrangement, such as a del(7q) and a t(12;14) rearrangement (4,5) . Previous studies suggested that two possible pathways are involved in the proliferation of uterine leiomyoma.…”

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confidence: 99%

Profiling of differentially expressed genes in human uterine leiomyomas

Lee¹,

Lee²,

Rho³

et al. 2005

Int J Gynecol Cancer

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Uterine leiomyomas are very common benign tumors resulting in clinically serious gynecological problems in women of reproductive age. Approximately, 1% of leiomyosarcoma was reported to arise in a preexisting leiomyoma. However, the molecular basis of these tumors is poorly understood. To understand the molecular changes during leiomyoma development, we profiled differentially expressed genes in ten paired leiomyoma and normal myometrial tissues using cDNA microarray chip analysis. We identified 67 genes (27 overexpressed and 40 underexpressed) which were scored as differentially expressed at least twofold in at least eight of ten patients. Eighteen of 67 genes have been already reported to be differentially expressed without their established functions in uterine leiomyoma and others have never been reported. Subsequently, the relative expression levels of representative genes from identified 67 genes were confirmed by reverse-transcriptase polymerase chain reaction and immunohistochemistry and were found to be consistent with the microarray data. This study could provide a new insight into the understanding of leiomyoma and leiomyosarcoma.

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Identification of a YAC spanning the translocation breakpoints in uterine leiomyomata, pulmonary chondroid hamartoma, and lipoma: physical mapping of the 12q14–q15 breakpoint region in uterine leiomyomata

Cited by 45 publications

References 27 publications

HMGA2 is associated with invasiveness but not a suitable marker for the detection of circulating tumor cells in breast cancer

HMGA2 is associated with invasiveness but not a suitable marker for the detection of circulating tumor cells in breast cancer

Transcriptional Activation of the Cyclin A Gene by the Architectural Transcription Factor HMGA2

Profiling of differentially expressed genes in human uterine leiomyomas

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