Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias

Ho Keun Yi, Yasuo Fujimura, Mamoru Oouchida, D. D K Prasad, Veena N. Rao, E. Shyam P Reddy

Research output: Contribution to journalArticle

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Abstract

Two ets family members, namely erg and Fli-1 are fused with two EWS familiy members namely EWS and TLS/FUS as a result of chromosome translocation in human solid tumors and leukemias. EWS-erg and EWS-Fli-1, which are involved in greater than 95% of Ewing family of tumors, were shown to function as transcriptional activators. TLS/FUS-erg, which is involved in human myeloid leukemias also functions as a transcriptional activator. Expression of these fusion proteins (EWS-erg and EWS-Fli-1) are shown to be essential for maintaining the oncogenic and tumorigenic properties of tumor cells. Cancer is thought to be caused not only by uncontrolled cell proliferation but also by deregulation of programmed cell death. Therefore, we have studied the role of normal (Fli-1 and erg) and aberrant fusion proteins (EWS-erg, EWS-Fli-1 and TLS/FUS-erg) in apoptosis. We have found that expression of normal (Fli-1 and erg) and aberrant fusion proteins inhibit the apoptosis of NIH3T3 cells induced by either serum deprivation or by treatment with calcium ionophore. We have also observed similar suppression of apoptosis in Ewing's sarcoma cells expressing EWS-Fli-1 and EWS-erg proteins suggesting that these fusion proteins may be responsible for the decreased ability of these tumor cells to undergo apoptosis. Inhibition of the expression of these aberrant fusion proteins by antisense RNA technique resulted in increased susceptibility to apoptosis leading to the death of tumor cells. Therefore, our results suggest that one can use therapeutic agents which can down regulate the expression of fusion proteins in combination with chemotherapeutic agents as an effective treatment for these human solid tumors and leukemias.

Original languageEnglish
Pages (from-to)1259-1268
Number of pages10
JournalOncogene
Volume14
Issue number11
Publication statusPublished - 1997
Externally publishedYes

Fingerprint

Leukemia
Apoptosis
RNA-Binding Protein EWS
Neoplasms
Proteins
Ewing's Sarcoma
RNA-Binding Protein FUS
Cell Death
Antisense RNA
Aptitude
Myeloid Leukemia
Calcium Ionophores
Therapeutic Uses
Inhibition (Psychology)
Down-Regulation
Chromosomes
Cell Proliferation
1-(2'-tetrahydrothienyl) 5-fluorouracil
Serum

Keywords

  • Apoptosis
  • Ewing's sarcoma
  • EWS- and TLS-fusion proteins
  • Human myeloid leukemias
  • Therapy

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Yi, H. K., Fujimura, Y., Oouchida, M., Prasad, D. D. K., Rao, V. N., & Reddy, E. S. P. (1997). Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias. Oncogene, 14(11), 1259-1268.

Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias. / Yi, Ho Keun; Fujimura, Yasuo; Oouchida, Mamoru; Prasad, D. D K; Rao, Veena N.; Reddy, E. Shyam P.

In: Oncogene, Vol. 14, No. 11, 1997, p. 1259-1268.

Research output: Contribution to journalArticle

Yi, HK, Fujimura, Y, Oouchida, M, Prasad, DDK, Rao, VN & Reddy, ESP 1997, 'Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias', Oncogene, vol. 14, no. 11, pp. 1259-1268.
Yi, Ho Keun ; Fujimura, Yasuo ; Oouchida, Mamoru ; Prasad, D. D K ; Rao, Veena N. ; Reddy, E. Shyam P. / Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias. In: Oncogene. 1997 ; Vol. 14, No. 11. pp. 1259-1268.
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