Loss of gfap expression in high-grade astrocytomas does not contribute to tumor development or progression

ABSTRACT In astrocytic neoplasms, the number of cells expressing glial fibrillary acidic protein (GFAP) is inversely proportional to the extent of anaplasia. The loss of GFAP expression, the

principal marker of astroglial cells, in these tumors has been proposed to constitute a step in their development and progression. To test this hypothesis, we crossed p53-negative

(_p53_−/−) mice, which frequently develop astrocytomas after intrauterine exposure to ethylnitrosourea, with GFAP-negative (_GFAP_−/−) mice or _GFAP_+/+ controls. Brain tumors of glial

origin were found in 12 of 35 _GFAP_+/+ _p53_−/− mice (34%) and in 11 of 27 _GFAP_−/− _p53_−/− mice (41%). The two groups did not differ in the age at which tumors were detected or in tumor

histology or progression. Thus, the loss of GFAP expression frequently seen in high-grade astrocytomas does not constitute a step in tumor development. Rather, it may represent the

undifferentiated state of these cells. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through

your institution Subscribe to this journal Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant

access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions *

Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS PDGF GENE EXPRESSION AND P53 ALTERATIONS CONTRIBUTE TO THE BIOLOGY OF DIFFUSE ASTROCYTIC GLIOMAS Article Open

access 25 February 2023 SUBEPENDYMAL GIANT CELL ASTROCYTOMAS ARE CHARACTERIZED BY MTORC1 HYPERACTIVATION, A VERY LOW SOMATIC MUTATION RATE, AND A UNIQUE GENE EXPRESSION PROFILE Article 13

October 2020 GLIOMA Article 09 May 2024 REFERENCES * Bigner SH, McLendon RE, Al-dosari N and Rasheed A . (1998). _The Genetic Basis of Human Cancer._ Vogelstein B and Kinsler KW (eds).

McGraw-Hill: New York, pp. 661–670. Google Scholar  * Chen WJ and Liem RK . (1994). _J. Cell Biol._, 127, 813–823. * Dalton S . (1992). _EMBO J._, 11, 1797–1804. * Deck JH, Eng LF, Bigbee J

and Woodcock SM . (1978). _Acta Neuropathol_. (Berl.), 42, 183–190. * Eliasson C, Sahlgren C, Berthold CH, Stakeberg J, Celis JE, Betsholtz C, Eriksson JE and Pekny M . (1999). _J. Biol.

Chem._, 274, 3996–4006. * Eng LF, Vanderhaeghen JJ, Bignami A and Gerstl G . (1971). _Brain Res._, 28, 351–354. * Eng LF and Rubinstein LJ . (1978). _J. Histochem. Cytochem._, 26, 513–522. *

Eng LF, Ghirnikar RS and Lee YL . (2000). _Neurochem. Res._, 25, 1439–1451. * Engebraaten O, Hjortland GO, Hirschberg H and Fodstad O . (1999). _J. Neurosurg._, 90, 125–132. * Hara A, Sakai

N, Yamada H, Niikawa S, Ohno T, Tanaka T and Mori H . (1991). _Surg. Neurol._, 36, 190–194. * Inagaki M, Gonda Y, Nishizawa K, Kitamura S, Sato C, Ando S, Tanabe K, Kikuchi K, Tsuiki S and

Nishi Y . (1990). _J. Biol. Chem._, 265, 4722–4729. * Jacque CM, Vinner C, Kujas M, Raoul M, Racadot J and Baumann NA . (1978). _J. Neurol. Sci._, 35, 147–155. * Jacque CM, Kujas M, Poreau

A, Raoul M, Collier P, Racadot J and Baumann N . (1979). _J. Natl. Cancer Inst._, 62, 479–483. * Kajiwara K, Orita T, Nishizaki T, Kamiryo T, Nakayama H and Ito H . (1992). _Brain Res._,

572, 314–318. * Ku NO, Liao J, Chou CF and Omary MB . (1996). _Cancer Metastasis Rev._, 15, 429–444. * Leonard JR, D'Sa C, Klocke BJ and Roth KA . (2001). _Oncogene_, 20, 8281–8286. *

Livingstone LR, White A, Sprouse J, Livanos E, Jacks T and Tlsty TD . (1992). _Cell_, 70, 923–935. * Oda H, Zhang S, Tsurutani N, Shimizu S, Nakatsuru Y, Aizawa S and Ishikawa T . (1997).

_Cancer Res._, 57, 646–650. * Pekny M, Levéen P, Pekna M, Eliasson C, Berthold C-H, Westermark B and Betsholtz C . (1995). _EMBO J._, 14, 1590–1598. * Pekny M, Eliasson C, Chien CL, Kindblom

LG, Liem R, Hamberger A and Betsholtz C . (1998). _Exp. Cell Res._, 239, 332–343. * Pekny M, Johansson CB, Eliasson C, Stakeberg J, Wallen A, Perlmann T, Lendahl U, Betsholtz C, Berthold CH

and Frisen J . (1999). _J. Cell Biol._, 145, 503–514. * Pekny M . (2001). _Prog. Brain Res._, 132, 23–30. * Rutka JT and Smith SL . (1993). _Cancer Res._, 53, 3624–3631. * Rutka JT, Hubbard

SL, Fukuyama K, Matsuzawa K, Dirks PB and Becker LE . (1994). _Cancer Res._, 54, 3267–3272. * Sidransky D, Mikkelsen T, Schwechheimer K, Rosenblum ML, Cavanee W and Vogelstein B . (1992).

_Nature_, 355, 846–847. * Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH and Tavtigian SV .

(1997). _Nat. Genet._, 15, 356–362. * Tascos NA, Parr J and Gonatas NK . (1982). _Hum. Pathol._, 13, 454–458. * Toda M, Miura M, Asou H, Toya S and Uyemura K . (1994). _J. Neurochem._, 63,

1975–1978. * Toda M, Miura M, Asou H, Sugiyama I, Kawase T and Uyemura K . (1999). _Neurochem. Res._, 24, 339–343. * Tsujimura K, Tanaka J, Ando S, Matsuoka Y, Kusubata M, Sugiura H,

Yamauchi T and Inagaki M . (1994). _J. Biochem._ (Tokyo), 116, 426–434. * van der Meulen JD, Houthoff HJ and Ebels EJ . (1978). _Neuropathol. Appl. Neurobiol._, 4, 177–190. * Velasco ME,

Dahl D, Roessmann U and Gambetti P . (1980). _Cancer_, 45, 484–494. * Wechsler W, Rice JM and Vesselinovitch SD . (1979). _Natl. Cancer Inst. Monogr._, 51, 219–226. * Weinstein DE, Shelanski

ML and Liem RK . (1991). _J. Cell. Biol._, 112, 1205–1213. * Weiss WA . (2000). _Curr. Opin. Pediatr._, 6, 543–548. * Westermark B . (1973). _Int. J. Cancer_, 12, 438–451. * Yahanda AM,

Bruner JM, Donehower LA and Morrison RS . (1995). _Mol. Cell. Biol._, 15, 4249–4259. * Yong VW . (1992). _J. Neurol. Sci._, 111, 92–103. * Zhu Y and Parada LF . (2002). _Nat. Rev. Cancer_,

8, 616–626. Download references ACKNOWLEDGEMENTS This article is dedicated to the memory of Professor Jan Pontén. We thank Dr Ricardo Feinstein (State Veterinary Institute, Uppsala, Sweden)

for help with characterization of the tumors, Professor Christer Betsholtz for valuable discussions, and Dr Marcela Pekna for critical reading of the manuscript. This study was supported by

grants from the Swedish Cancer Foundation (project no. 3622), the Swedish Medical Research Council (project no. 11548), the Swedish Society for Medicine, the Swedish Society for Medical

Research, the King Gustaf V Foundation, Volvo Assar Gabrielsson Fond, and the Swedish Stroke Foundation. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Medical Biochemistry,

Göteborg University, Box 440, Göteborg, SE-405 30, Sweden Ulrika Wilhelmsson, Camilla Eliasson & Milos Pekny * Department of Anatomy and Cell Biology, Bergen University, Bergen, Norway

Rolf Bjerkvig Authors * Ulrika Wilhelmsson View author publications You can also search for this author inPubMed Google Scholar * Camilla Eliasson View author publications You can also

search for this author inPubMed Google Scholar * Rolf Bjerkvig View author publications You can also search for this author inPubMed Google Scholar * Milos Pekny View author publications You

can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Milos Pekny. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE Wilhelmsson, U., Eliasson, C., Bjerkvig, R. _et al._ Loss of GFAP expression in high-grade astrocytomas does not contribute to tumor development or progression. _Oncogene_ 22,

3407–3411 (2003). https://doi.org/10.1038/sj.onc.1206372 Download citation * Received: 30 August 2002 * Revised: 19 November 2002 * Accepted: 09 January 2003 * Published: 29 May 2003 * Issue

Date: 29 May 2003 * DOI: https://doi.org/10.1038/sj.onc.1206372 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a

shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * glial fibrillary acidic protein *

astrocytoma * intermediate filaments * gene targeting * p53