Expression of the HMGI(Y) Gene Products in Human Neuroblastic Tumours Correlates with Differentiation Status

Overview

Journal Br J Cancer

Specialty Oncology

Date 2000 Nov 15

PMID 11076660

Citations 17

Authors

G Giannini

C J Kim

L Di Marcotullio

G Manfioletti

B Cardinali

F Cerignoli

E Ristori

M Zani

L Frati

I Screpanti

A Guilino

Affiliations

Soon will be listed here.

Abstract

HMGI and HMGY are splicing variants of the HMGI(Y) gene and together with HMGI-C, belong to a family of DNA binding proteins involved in maintaining active chromatin conformation and in the regulation of gene transcription. The expression of the HMGI(Y) gene is maximal during embryonic development, declines in adult differentiated tissues and is reactivated in most transformed cells in vitro and in many human cancers in vivo. The HMGI(Y) genomic locus is frequently rearranged in mesenchymal tumours, suggesting a biological role for HMGI(Y) gene products in tumour biology. HMGIs are both target and modulators of retinoic acid activity. In fact, HMGI(Y) gene expression is differentially regulated by retinoic acid in retinoid-sensitive and -resistant neuroblastoma cells, while HMGI-C participates in conferring retinoic acid resistance in some neuroblastoma cells. In this paper we show that HMGI and HMGY isoforms are equally regulated by retinoic acid in neuroblastoma cell lines at both RNA and protein levels. More importantly our immunohistochemical analysis shows that, although HMGI(Y) is expressed in all neuroblastic tumours, consistently higher levels are observed in less differentiated neuroblastomas compared to more differentiated ganglioneuromas, indicating that HMGI(Y) expression should be evaluated as a potential diagnostic and prognostic marker in neuroblastic tumours.

Citing Articles

A gene dosage-dependent effect unveils NBS1 as both a haploinsufficient tumour suppressor and an essential gene for SHH-medulloblastoma.

Petroni M, Fabretti F, Di Giulio S, Nicolis di Robilant V, La Monica V, Moretti M Neuropathol Appl Neurobiol. 2022; 48(6):e12837.

PMID: 35839783 PMC: 9542137. DOI: 10.1111/nan.12837.

A combination of PARP and CHK1 inhibitors efficiently antagonizes MYCN-driven tumors.

Di Giulio S, Colicchia V, Pastorino F, Pedretti F, Fabretti F, Nicolis di Robilant V Oncogene. 2021; 40(43):6143-6152.

PMID: 34508175 PMC: 8553625. DOI: 10.1038/s41388-021-02003-0.

HMGA1 Induction of miR-103/107 Forms a Negative Feedback Loop to Regulate Autophagy in MPTP Model of Parkinson's Disease.

Li G, Luo W, Wang B, Qian C, Ye Y, Li Y Front Cell Neurosci. 2021; 14:620020.

PMID: 33536877 PMC: 7847849. DOI: 10.3389/fncel.2020.620020.

High-mobility group AT-hook 1 promotes cardiac dysfunction in diabetic cardiomyopathy via autophagy inhibition.

Wu Q, Liu C, Cai Z, Xie Q, Hu T, Duan M Cell Death Dis. 2020; 11(3):160.

PMID: 32123163 PMC: 7052237. DOI: 10.1038/s41419-020-2316-4.

miRNA expression changes during the course of neoadjuvant bevacizumab and chemotherapy treatment in breast cancer.

Lindholm E, Aure M, Haugen M, Sahlberg K, Kristensen V, Nebdal D Mol Oncol. 2019; 13(10):2278-2296.

PMID: 31402562 PMC: 6763780. DOI: 10.1002/1878-0261.12561.

References

Matthay K, Villablanca J, Seeger R, Stram D, Harris R, Ramsay N . Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children's Cancer Group. N Engl J Med. 1999; 341(16):1165-73. DOI: 10.1056/NEJM199910143411601. View

Battista S, Fidanza V, Fedele M, Klein-Szanto A, Outwater E, Brunner H . The expression of a truncated HMGI-C gene induces gigantism associated with lipomatosis. Cancer Res. 1999; 59(19):4793-7. View

Pedeutour F, Quade B, Sornberger K, Tallini G, Ligon A, Weremowicz S . Dysregulation of HMGIC in a uterine lipoleiomyoma with a complex rearrangement including chromosomes 7, 12, and 14. Genes Chromosomes Cancer. 1999; 27(2):209-15. View

ARLOTTA P, Tai A, Manfioletti G, Clifford C, Jay G, Ono S . Transgenic mice expressing a truncated form of the high mobility group I-C protein develop adiposity and an abnormally high prevalence of lipomas. J Biol Chem. 2000; 275(19):14394-400. DOI: 10.1074/jbc.m000564200. View

Thiele C, Reynolds C, Israel M . Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma. Nature. 1985; 313(6001):404-6. DOI: 10.1038/313404a0. View

Seeger R, Brodeur G, Sather H, Dalton A, Siegel S, Wong K . Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med. 1985; 313(18):1111-6. DOI: 10.1056/NEJM198510313131802. View

BOLANDE R . Spontaneous regression and cytodifferentiation of cancer in early life: the oncogenic grace period. Surv Synth Pathol Res. 1985; 4(4):296-311. DOI: 10.1159/000156982. View

Giancotti V, Pani B, DAndrea P, Berlingieri M, Di Fiore P, Fusco A . Elevated levels of a specific class of nuclear phosphoproteins in cells transformed with v-ras and v-mos oncogenes and by cotransfection with c-myc and polyoma middle T genes. EMBO J. 1987; 6(7):1981-7. PMC: 553586. DOI: 10.1002/j.1460-2075.1987.tb02461.x. View

Abemayor E, Sidell N . Human neuroblastoma cell lines as models for the in vitro study of neoplastic and neuronal cell differentiation. Environ Health Perspect. 1989; 80:3-15. PMC: 1567609. DOI: 10.1289/ehp.89803. View

10.

Johnson K, Lehn D, Reeves R . Alternative processing of mRNAs encoding mammalian chromosomal high-mobility-group proteins HMG-I and HMG-Y. Mol Cell Biol. 1989; 9(5):2114-23. PMC: 363005. DOI: 10.1128/mcb.9.5.2114-2123.1989. View

11.

Thiele C . Pediatric peripheral neuroectodermal tumors, oncogenes, and differentiation. Cancer Invest. 1990; 8(6):629-39. DOI: 10.3109/07357909009018932. View

12.

Manfioletti G, Giancotti V, Bandiera A, Buratti E, Sautiere P, Cary P . cDNA cloning of the HMGI-C phosphoprotein, a nuclear protein associated with neoplastic and undifferentiated phenotypes. Nucleic Acids Res. 1991; 19(24):6793-7. PMC: 329311. DOI: 10.1093/nar/19.24.6793. View

13.

Finklestein J, Krailo M, Lenarsky C, Ladisch S, Blair G, Reynolds C . 13-cis-retinoic acid (NSC 122758) in the treatment of children with metastatic neuroblastoma unresponsive to conventional chemotherapy: report from the Childrens Cancer Study Group. Med Pediatr Oncol. 1992; 20(4):307-11. DOI: 10.1002/mpo.2950200407. View

14.

Giancotti V, Bandiera A, Ciani L, Santoro D, Crane-Robinson C, Goodwin G . High-mobility-group (HMG) proteins and histone H1 subtypes expression in normal and tumor tissues of mouse. Eur J Biochem. 1993; 213(2):825-32. DOI: 10.1111/j.1432-1033.1993.tb17825.x. View

15.

Friedmann M, Holth L, Zoghbi H, Reeves R . Organization, inducible-expression and chromosome localization of the human HMG-I(Y) nonhistone protein gene. Nucleic Acids Res. 1993; 21(18):4259-67. PMC: 310059. DOI: 10.1093/nar/21.18.4259. View

16.

Berlingieri M, Manfioletti G, Santoro M, Bandiera A, Visconti R, Giancotti V . Inhibition of HMGI-C protein synthesis suppresses retrovirally induced neoplastic transformation of rat thyroid cells. Mol Cell Biol. 1995; 15(3):1545-53. PMC: 230378. DOI: 10.1128/MCB.15.3.1545. View

17.

Chiappetta G, Bandiera A, Berlingieri M, Visconti R, Manfioletti G, Battista S . The expression of the high mobility group HMGI (Y) proteins correlates with the malignant phenotype of human thyroid neoplasias. Oncogene. 1995; 10(7):1307-14. View

18.

Zhou X, Benson K, Ashar H, Chada K . Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C. Nature. 1995; 376(6543):771-4. DOI: 10.1038/376771a0. View

19.

Schoenmakers E, Wanschura S, Mols R, Bullerdiek J, Van Den Berghe H, Van de Ven W . Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours. Nat Genet. 1995; 10(4):436-44. DOI: 10.1038/ng0895-436. View

20.

Fedele M, Bandiera A, Chiappetta G, Battista S, Viglietto G, Manfioletti G . Human colorectal carcinomas express high levels of high mobility group HMGI(Y) proteins. Cancer Res. 1996; 56(8):1896-901. View