Tumor Suppression

Studies from University of Athens provide new data on non-small cell lung cancer

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"Although ZBTB7A expression has been found to be increased in various types of lymphoma, there are no reports dealing with its expression in solid tumours. Given that p14(ARF) inhibits MDM2, the main negative regulator of p53, we hypothesized that overexpression of ZBTB7A could lead indirectly to p53 inactivation. To this end, we examined the status of ZBTB7A and its relationship with tumor kinetics (proliferation and apoptosis) and nodal members of the p53 network in a panel of 83 non-small cell lung carcinomas (NSCLCs). We observed, in the majority of the samples, prominent expression of ZBTB7A in the cancerous areas compared to negligible presence in the adjacent normal tissue elements. Gene amplification (two-to five-fold) was found in 27.7% of the cases, denoting its significance as a mechanism driving ZBTB7A overproduction in NSCLCs. In the remaining non-amplified group of carcinomas, analysis of the mRNA and protein expression patterns suggested that deregulation at the transcriptional and post-translational level accounts for ZBTB7A overexpression. Proliferation was associated with ZBTB7A expression (p=0.033) but not apoptosis. The association with proliferation was reflected in the positive correlation between ZBTB7A expression and tumor size (p=0.018). The overexpression of ZBTB7A in both p53 mutant and p53 wild-type cases, implies either a synergistic effect or that ZBTB7A exerts its oncogenic properties independently of the p14(ARF)-MDM2-p53 axis," wrote K. Apostolopoulou and colleagues, University of Athens.

The researchers concluded: "The concomitant expression of ZBTB7A with p14(ARF) (p=0.039), instead of the anticipated inverse relation, supports the latter notionregardless of the pathway followed, the distinct expression of ZBTB7A in cancerous areas and the association with proliferation and tumor size pinpoints a role for this novel cell cycle regulator in the pathogenesis of lung cancer."

Apostolopoulou and colleagues published their study in the Journal of Pathology (Gene amplification is a relatively frequent event leading to ZBTB7A (Pokemon) overexpression in non-small cell lung cancer. Journal of Pathology, 2007;213(3):294-302).

For additional information, contact K. Apostolopoulou, University of Athens, Molecular Carcinogenesis Group, Laboratory of Histology-Embryology, Medical School, Athens, Greece.

Publisher contact information for the Journal of Pathology is: John Wiley & Sons Ltd., the Atrium, Southern Gate, Chichester PO19 8SQ, W Sussex, England.

Keywords: Greece, Athens, Biotechnology, Gene Therapy, Genetics, Genomics, Lung Neoplasms, Non-Small Cell Lung Cancer, Non-Small Cell Lung Carcinoma, Oncology, Pathology, Tumor Suppression.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2007, Clinical Oncology Week via NewsRx.com.