BMP4 increases expression of HMGA2 in mesenchymal stem cells.

BMP4 has been linked to early steps of adipocyte lineage differentiation but only little is known about its corresponding downstream pathways. Herein, we have investigated whether or not the expression of high mobility group protein HMGA2, another protein linked to proliferation and differentiation within the process of adipogenesis, may be influenced by BMP4 signaling in adipose tissue derived stem cells. Compared to FGF1, a strong inducer of HMGA2 in immortalized pre-adipocytes, BMP4 was found moderately to induce the HMGA2 mRNA expression in serum starved adipose tissue derived stem cells and myometrial cells.

p14Arf acts as an antagonist of HMGA2 in senescence of mesenchymal stem cells-implications for benign tumorigenesis.

HMGA2 is a major regulator of benign tumorigenesis from mesenchyme-derived tissues and stem-cell self-renewal. It has been postulated that HMGA2 mediates its critical function by decreasing p16(Ink4a)/p14(Arf) expression and cellular senescence. To repress the oncogenic activity of HMGA2, the lin-28-let-7 axis is thought to increasingly repress the expression of HMGA2 with age.

HMGA2 and the p19Arf-TP53-CDKN1A axis: a delicate balance in the growth of uterine leiomyomas.

Pathogenetically, uterine leiomyomas (ULs) can be interpreted as the result of a monoclonal abnormal proliferation of myometrial cells. Oncogene-induced senescence (OIS) is a frequent phenomenon in premalignant lesions that leads to a growth arrest mainly by the activation of two potent growth-inhibitory pathways as represented by p16(Ink4a) and p19(Arf). The relevance of OIS for the development of UL has not been addressed, but HMGA2, encoded by a major target gene of recurrent chromosomal abnormalities in UL, has been implicated in the repression of the Ink4a/Arf (CDKN2A) locus.

A microRNA encoded in a highly conserved part of the mammalian HMGA2 gene.

The high mobility group protein HMGA2 plays an important role as a chromatin component of stem cells and as a protein causally related to the development of a variety of benign tumors (e.g., uterine leiomyomas, lipomas, and pleomorphic adenomas of the salivary glands).

Germ line mutations of the HMGA2 gene are rare among the general population.

Proteins encoded by the HMGA family are architectural transcription factors, which induce conformational changes in the DNA and thus influence gene expression. Despite the obvious association of the expression of high mobility group protein genes with human cancer, very little is known about the variation of the HMGA proteins within human populations. Therefore, the coding regions of HMGA2 from 87 normal healthy donors were sequenced with the aim of detecting single nucleotide polymorphisms.

Expression patterns of the LPP-HMGA2 fusion transcript in pulmonary chondroid hamartomas with t(3;12)(q27 approximately 28;q14 approximately 15).

The high frequency of the t(3;12)(q27 approximately 28; q14 approximately 15) in lipomas and pulmonary chondroid hamartomas (PCHs) makes the HMGA2-LPP fusion gene the most frequent fusion gene in human tumors. We analyzed 11 PCHs with a t(3;12)(q27 approximately 28;q14 approximately 15) for the expression of the LPP-HMGA2 fusion transcript. In a previous study, all of these tumors were shown to express the HMGA2-LPP fusion transcript, composed of exons 1-3 of HMGA2 and exons 9-11 of LPP.