HMGA1 protein expression in familial breast carcinoma patients

Chiappetta, Gennaro; Ottaiano, Alessandro; Vuttariello, Emilia; Monaco, Mario; Galdiero, Francesca; Gallipoli, Adolfo; Pilotti, Silvana; Jodice, Giovanna; Manoukian, Siranoush; Colombo, Mara; Ripamonti, Carla; Pallante, P; Radice, Paolo; Fusco, Alfredo

doi:10.1016/j.ejca.2009.10.015

Cited by 19 publications

(9 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The HMGA family includes the products of the HMGA1 and HMGA2 genes. HMGA1 has been found to be abnormally expressed in several types of malignant tumors, including breast (43)(44)(45), ovarian (46), leukemia (47), colon (48), pancreatic (49), thyroid (50), lung (51), prostate (52), endometrial (53), and head and neck malignant tumor (54).…”

Section: Discussionmentioning

confidence: 99%

Let-7a inhibits growth and migration of breast cancer cells by targeting HMGA1

Liu

Zhang

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Let-7 is one of the earliest discovered microRNAs (miRNAs) and has been reported to regulate self renewal and tumorigenicity of breast cancer cells. Let-7a is a member of this family and its function has not been fully characterized in breast cancer. First, total RNAs of breast cancer cells (MDA-MB-231, MCF-7), breast cancer tissues and corresponding adjacent normal tissues were extracted and used to detect let-7a expression by qRT-PCR. Secondly, the effects of let-7a on proliferation, colony formation, migration and invasion of breast cancer cells were assessed by in vitro cell culture experiments. Finally, western blotting was performed to demonstrate how let-7a regulated HMGA1 expression. We found that let-7a expression was significantly lower in breast cancer cells and breast cancer tissues compared to corresponding adjacent normal tissues. Cell proliferation, colony formation, migration and invasion were decreased after overexpression of let-7a in breast cancer cells and vice versa. Furthermore, we identified the high mobility group A1 (HMGA1) as a potential target gene of let-7a. Protein expression of the target gene was significantly downregulated in let-7a mimic transfected breast cancer cells and significantly upregulated in let-7a inhibitor transfected breast cancer cells. Our data suggest that let-7a plays an important role as a tumor suppressor gene by targeting HMGA1, which may open novel perspectives for clinical treatments against breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Let-7a inhibits growth and migration of breast cancer cells by targeting HMGA1

Liu

Zhang

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…Many immediate- and delayed-early genes are required by cells to traverse the G1/S boundary of the cell cycle and function as oncogenes when aberrantly expressed. Further studies uncovered high levels of HMGA1 expression at the mRNA or protein level in human cancer cells or primary tumors from diverse tissues, including thyroid [45–48], lung [49–51], breast [52–59, 117], bladder [58], prostate [60–62], colon [63–68], pancreas [69–74], uterine corpus [75], uterine cervix [76], kidney [77], head and neck [78], nervous system [58, 79–84], stomach [85, 86], liver [87], and hematopoietic system [88–93, 118, 119]. HMGA1 expression is low or undetectable in normal tissue counterparts.…”

Section: Hmga1 Is Up-regulated In Rapidly Proliferating Cells and Camentioning

confidence: 99%

The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development

Sumter¹,

Xian²,

Huso³

et al. 2016

CMM

103

View full text Add to dashboard Cite

Background & Objectives Chromatin structure is the single most important feature that distinguishes a cancer cell from a normal cell histologically. Chromatin remodeling proteins regulate chromatin structure and high mobility group A (HMGA1) proteins are among the most abundant, nonhistone chromatin remodeling proteins found in cancer cells. These proteins include HMGA1a/HMGA1b isoforms, which result from alternatively spliced mRNA. The HMGA1 gene is overexpressed in cancer and high levels portend a poor prognosis in diverse tumors. HMGA1 is also highly expressed during embryogenesis and postnatally in adult stem cells. Overexpression of HMGA1 drives neoplastic transformation in cultured cells, while inhibiting HMGA1 blocks oncogenic and cancer stem cell properties. Hmga1 transgenic mice succumb to aggressive tumors, demonstrating that dysregulated expression of HMGA1 causes cancer in vivo. HMGA1 is also required for reprogramming somatic cells into induced pluripotent stem cells. HMGA1 proteins function as ancillary transcription factors that bend chromatin and recruit other transcription factors to DNA. They induce oncogenic transformation by activating or repressing specific genes involved in this process and an HMGA1 “transcriptome” is emerging. Although prior studies reveal potent oncogenic properties of HMGA1, we are only beginning to understand the molecular mechanisms through which HMGA1 functions. In this review, we summarize the list of putative downstream transcriptional targets regulated by HMGA1. We also briefly discuss studies linking HMGA1 to Alzheimer’s disease and type-2 diabetes. Conclusion Further elucidation of HMGA1 function should lead to novel therapeutic strategies for cancer and possibly for other diseases associated with aberrant HMGA1 expression.

show abstract

“…Increasing evidence suggests that HMGA1 protein functions as a master regulator with a critical role in normal development and tumor progression in diverse malignancies [10]. A plethora of reports has been published demonstrating that HMGA1 protein is undetectable in normal tissues, but expressed at high levels in diverse human cancer cells, including cancers of the thyroid [11], breast [12], cervix [13], gastric mucosa [14], skin [15], colon [16], liver [17], pancreas [18], hematopoietic system [19], lung [20] as well as in neuroblastoma [21] of the central nervous system. The oncogenic effects of HMGA1 are likely related to its ability to activate expression of various genes that promote cell proliferation and invasion or prevent apoptotic cell death.…”

Section: Introductionmentioning

confidence: 99%