• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of amjpatholAmerican Journal of Pathology For AuthorsAmerican Journal of Pathology SubscribeAmerican Journal of Pathology SearchAmerican Journal of Pathology Current IssueAmerican Journal of Pathology About the JournalAmerican Journal of Pathology
Am J Pathol. Mar 1997; 150(3): 911–918.
PMCID: PMC1857869

HMGI(Y) expression in human uterine leiomyomata. Involvement of another high-mobility group architectural factor in a benign neoplasm.

Abstract

Chromosomal rearrangements involving 6p21 have been observed in uterine leiomyomata and a variety of other benign tumors. The gene for HMGI(Y), a member of the high-mobility group (HMG) family of proteins, has been localized to 6p21. To determine whether rearrangements observed in this area alter HMGI(Y) expression, we analyzed HMGI(Y) DNA-binding activity in protein extracts from uterine leiomyoma and normal myometrium tissues. This report describes a uterine leiomyoma specimen with an inv(6)(p21q15). A genomic P1 clone that contains the HMGI(Y) region of chromosome 6 is found to span the inversion breakpoint by fluorescent in situ hybridization of metaphase chromosomes. Expression of HMGI(Y) protein in this leiomyoma specimen is increased dramatically as compared with the matching normal myometrial tissue. Elevated HMGI(Y) expression was also found in 8 of 16 leiomyomas without cytogenetically detectable chromosome 6p21 aberrations but not in any of the 9 matching myometrial tissues. Analysis of the genetic events involved in the pathobiology of these benign tumors will provide a basis for understanding the process of improper cellular growth and might be important in deciphering the multistep pathway of tumorigenesis.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol. 1990 Oct;94(4):435–438. [PubMed]
  • Nibert M, Heim S. Uterine leiomyoma cytogenetics. Genes Chromosomes Cancer. 1990 May;2(1):3–13. [PubMed]
  • Rein MS, Friedman AJ, Barbieri RL, Pavelka K, Fletcher JA, Morton CC. Cytogenetic abnormalities in uterine leiomyomata. Obstet Gynecol. 1991 Jun;77(6):923–926. [PubMed]
  • Dal Cin P, Moerman P, Deprest J, Brosens I, Van den Berghe H. A new cytogenetic subgroup in uterine leiomyoma is characterized by a deletion of the long arm of chromosome 3. Genes Chromosomes Cancer. 1995 Jul;13(3):219–220. [PubMed]
  • Ashar HR, Fejzo MS, Tkachenko A, Zhou X, Fletcher JA, Weremowicz S, Morton CC, Chada K. Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains. Cell. 1995 Jul 14;82(1):57–65. [PubMed]
  • Schoenmakers EF, Wanschura S, Mols R, Bullerdiek J, Van den Berghe H, Van de Ven WJ. Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours. Nat Genet. 1995 Aug;10(4):436–444. [PubMed]
  • Kazmierczak B, Rosigkeit J, Wanschura S, Meyer-Bolte K, Van de Ven WJ, Kayser K, Krieghoff B, Kastendiek H, Bartnitzke S, Bullerdiek J. HMGI-C rearrangements as the molecular basis for the majority of pulmonary chondroid hamartomas: a survey of 30 tumors. Oncogene. 1996 Feb 1;12(3):515–521. [PubMed]
  • Schoenberg Fejzo M, Ashar HR, Krauter KS, Powell WL, Rein MS, Weremowicz S, Yoon SJ, Kucherlapati RS, Chada K, Morton CC. Translocation breakpoints upstream of the HMGIC gene in uterine leiomyomata suggest dysregulation of this gene by a mechanism different from that in lipomas. Genes Chromosomes Cancer. 1996 Sep;17(1):1–6. [PubMed]
  • Friedmann M, Holth LT, Zoghbi HY, Reeves R. Organization, inducible-expression and chromosome localization of the human HMG-I(Y) nonhistone protein gene. Nucleic Acids Res. 1993 Sep 11;21(18):4259–4267. [PMC free article] [PubMed]
  • Ozisik YY, Meloni AM, Altungoz O, Surti U, Sandberg AA. Translocation (6;10)(p21;q22) in uterine leiomyomas. Cancer Genet Cytogenet. 1995 Feb;79(2):136–138. [PubMed]
  • Heim S, Mandahl N, Kristoffersson U, Mitelman F, Röser B, Rydholm A, Willén H. Structural chromosome aberrations in a case of angioleiomyoma. Cancer Genet Cytogenet. 1986 Feb 15;20(3-4):325–330. [PubMed]
  • Fletcher JA, Pinkus JL, Lage JM, Morton CC, Pinkus GS. Clonal 6p21 rearrangement is restricted to the mesenchymal component of an endometrial polyp. Genes Chromosomes Cancer. 1992 Oct;5(3):260–263. [PubMed]
  • Sreekantaiah C, Leong SP, Karakousis CP, McGee DL, Rappaport WD, Villar HV, Neal D, Fleming S, Wankel A, Herrington PN, et al. Cytogenetic profile of 109 lipomas. Cancer Res. 1991 Jan 1;51(1):422–433. [PubMed]
  • Xiao S, Lux ML, Reeves R, Hudson TJ, Fletcher JA. HMGI(Y) activation by chromosome 6p21 rearrangements in multilineage mesenchymal cells from pulmonary hamartoma. Am J Pathol. 1997 Mar;150(3):901–910. [PMC free article] [PubMed]
  • Fletcher JA, Kozakewich HP, Hoffer FA, Lage JM, Weidner N, Tepper R, Pinkus GS, Morton CC, Corson JM. Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors. N Engl J Med. 1991 Feb 14;324(7):436–442. [PubMed]
  • Thanos D, Maniatis T. The high mobility group protein HMG I(Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene. Cell. 1992 Nov 27;71(5):777–789. [PubMed]
  • Finco TS, Baldwin AS. Mechanistic aspects of NF-kappa B regulation: the emerging role of phosphorylation and proteolysis. Immunity. 1995 Sep;3(3):263–272. [PubMed]
  • John S, Reeves RB, Lin JX, Child R, Leiden JM, Thompson CB, Leonard WJ. Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins. Mol Cell Biol. 1995 Mar;15(3):1786–1796. [PMC free article] [PubMed]
  • Du W, Thanos D, Maniatis T. Mechanisms of transcriptional synergism between distinct virus-inducible enhancer elements. Cell. 1993 Sep 10;74(5):887–898. [PubMed]
  • Whitley MZ, Thanos D, Read MA, Maniatis T, Collins T. A striking similarity in the organization of the E-selectin and beta interferon gene promoters. Mol Cell Biol. 1994 Oct;14(10):6464–6475. [PMC free article] [PubMed]
  • Wood LD, Farmer AA, Richmond A. HMGI(Y) and Sp1 in addition to NF-kappa B regulate transcription of the MGSA/GRO alpha gene. Nucleic Acids Res. 1995 Oct 25;23(20):4210–4219. [PMC free article] [PubMed]
  • Abdulkadir SA, Krishna S, Thanos D, Maniatis T, Strominger JL, Ono SJ. Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression. J Exp Med. 1995 Aug 1;182(2):487–500. [PMC free article] [PubMed]
  • Falvo JV, Thanos D, Maniatis T. Reversal of intrinsic DNA bends in the IFN beta gene enhancer by transcription factors and the architectural protein HMG I(Y). Cell. 1995 Dec 29;83(7):1101–1111. [PubMed]
  • Thanos D, Maniatis T. Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell. 1995 Dec 29;83(7):1091–1100. [PubMed]
  • Chuvpilo S, Schomberg C, Gerwig R, Heinfling A, Reeves R, Grummt F, Serfling E. Multiple closely-linked NFAT/octamer and HMG I(Y) binding sites are part of the interleukin-4 promoter. Nucleic Acids Res. 1993 Dec 11;21(24):5694–5704. [PMC free article] [PubMed]
  • Kim J, Reeves R, Rothman P, Boothby M. The non-histone chromosomal protein HMG-I(Y) contributes to repression of the immunoglobulin heavy chain germ-line epsilon RNA promoter. Eur J Immunol. 1995 Mar;25(3):798–808. [PubMed]
  • Zhao K, Käs E, Gonzalez E, Laemmli UK. SAR-dependent mobilization of histone H1 by HMG-I/Y in vitro: HMG-I/Y is enriched in H1-depleted chromatin. EMBO J. 1993 Aug;12(8):3237–3247. [PMC free article] [PubMed]
  • Lewin B. Chromatin and gene expression: constant questions, but changing answers. Cell. 1994 Nov 4;79(3):397–406. [PubMed]
  • Giancotti V, Bandiera A, Ciani L, Santoro D, Crane-Robinson C, Goodwin GH, Boiocchi M, Dolcetti R, Casetta B. High-mobility-group (HMG) proteins and histone H1 subtypes expression in normal and tumor tissues of mouse. Eur J Biochem. 1993 Apr 15;213(2):825–832. [PubMed]
  • Ram TG, Reeves R, Hosick HL. Elevated high mobility group-I(Y) gene expression is associated with progressive transformation of mouse mammary epithelial cells. Cancer Res. 1993 Jun 1;53(11):2655–2660. [PubMed]
  • Tamimi Y, van der Poel HG, Denyn MM, Umbas R, Karthaus HF, Debruyne FM, Schalken JA. Increased expression of high mobility group protein I(Y) in high grade prostatic cancer determined by in situ hybridization. Cancer Res. 1993 Nov 15;53(22):5512–5516. [PubMed]
  • Chiappetta G, Bandiera A, Berlingieri MT, Visconti R, Manfioletti G, Battista S, Martinez-Tello FJ, Santoro M, Giancotti V, Fusco A. The expression of the high mobility group HMGI (Y) proteins correlates with the malignant phenotype of human thyroid neoplasias. Oncogene. 1995 Apr 6;10(7):1307–1314. [PubMed]
  • Fedele M, Bandiera A, Chiappetta G, Battista S, Viglietto G, Manfioletti G, Casamassimi A, Santoro M, Giancotti V, Fusco A. Human colorectal carcinomas express high levels of high mobility group HMGI(Y) proteins. Cancer Res. 1996 Apr 15;56(8):1896–1901. [PubMed]
  • Sargent MS, Weremowicz S, Rein MS, Morton CC. Translocations in 7q22 define a critical region in uterine leiomyomata. Cancer Genet Cytogenet. 1994 Oct;77(1):65–68. [PubMed]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...