Source: Annual Congress 2002 - Thoracic oncology: biology
Disease area: Thoracic oncology

Abstract

The retinoblastoma family consists of the tumor suppressor pRb/p105 and related proteins p107 and pRb2/p130. Recent immunohistochemical studies in 235 specimens of lung cancer showed the tightest inverse association between the histological grading in the most aggressive tumor types and RB2/p130 protein expression.
This led us to study a panel of human lung cancers for mutations in the RB2/p130 gene, detected in primary lung tumors by single-strand conformation polymorphism and sequence analysis. Moreover a retroviral-mediated delivery of wild-type RB2/p130 to the lung tumor cell line H23 potently inhibited tumorigenesis in vitro and in vivo, as shown by the dramatic growth arrest observed in a colony assay and the suppression of anchorage-independent growth potential and tumor formation in nude mice. The tumors transduced with the RB2/p130 retrovirus diminished in size after a single injection and a 12-fold reduction in tumor growth after RB2/p130 transduction compared with the Pac-transduced tumors (92% reduction, P = .003) and lacZ-transduced tumors (93% reduction, P < .001) was found to be statistically significant.
These findings provide the missing confirmation that RB2/p130 is a [dsquote]bona fide[dsquote] tumor suppressor gene and strengthen the hypothesis that it may be a candidate for cancer gene therapy for lung cancer.

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A. A. Mancini, V. V. Esposito, A. A. De Luca, P. P. P. P. Claudio, A. M. A. M. Groeger, A. A. Giordamo, M. M. Caputi (Naples, Italy; Philadelphia, United States Of America). Mutations in the retinoblastoma-related gene RB2/p130 in lung tumours and suppression of tumour growth in vivo by retrovirus-mediated gene transfer. Eur Respir J 2002; 20: Suppl. 38, 143

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