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Overexpression of E2F1 associated with LOH at RB locus and hyperphosphorylation of RB in non-small cell lung carcinoma

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Abstract

Purpose

E2F1 plays a critical role in cell proliferation, and its function is controlled by the retinoblastoma (RB) protein. We examined the expression of E2F1 and the aberration of RB gene and protein to elucidate what factors contribute to the overexpression of E2F1 in non-small cell lung carcinomas.

Methods

The expression level of E2F1 in tissues of non-small cell lung carcinomas was measured by means of quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. For RB, we examined loss of heterozygosity (LOH) by PCR-restriction fragment length polymorphism and a variable number of tandem repeats, and protein expression by immunohistochemistry.

Results

Fifteen cases of carcinoma (46%) showed high transcription levels of E2F1 gene. Immunohistochemically, almost all (14 of 15) cases overexpressing E2F1 mRNA were positive for E2F1 protein. LOH at the RB locus was found in 13 of 30 informative cases. In 13 cases with LOH, ten showed overexpression of E2F1 mRNA and protein. Immunohistochemical positivity for phosphorylated RB protein was also closely correlated with overexpression of E2F1.

Conclusions

Our results suggest that overexpression of E2F1, induced both by LOH at the RB locus and anomalous phosphorylation of the RB protein, is involved in the development of non-small cell lung carcinoma.

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Authors and Affiliations

  1. Department of Laboratory Sciences, School of Health Sciences, Kanazawa University Faculty of Medicine, 5-11-80 Kodatsuno, 920-0942, Kanazawa , Japan

    Ei Kawahara

  2. Department of Health Science, Ishikawa Prefectural Nursing University, Kahoku-shi, Ishikawa, Japan

    Miwa Akasofu Imai

  3. Department of Pathology, School of Medicine, Kanazawa University Faculty of Medicine, Kanazawa, Japan

    Yoshio Oda

  4. Department of Surgery, School of Medicine, Kanazawa University Faculty of Medicine, Kanazawa, Japan

    Makoto Oda

  5. Kanazawa Laboratories, ALP, Kanazawa, Japan

    Isao Nakanishi

Authors
  1. Miwa Akasofu Imai
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  2. Yoshio Oda
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  3. Makoto Oda
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  4. Isao Nakanishi
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  5. Ei Kawahara
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Correspondence to Ei Kawahara.

Additional information

This work was supported by grants from the Japan Ministry of Education, Culture, Sports, Science and Technology

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Imai, M.A., Oda, Y., Oda, M. et al. Overexpression of E2F1 associated with LOH at RB locus and hyperphosphorylation of RB in non-small cell lung carcinoma. J Cancer Res Clin Oncol 130, 320–326 (2004). https://doi.org/10.1007/s00432-003-0538-3

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  • DOI: https://doi.org/10.1007/s00432-003-0538-3

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