ISSN 0891-4168, Molecular Genetics, Microbiology and Virology, 2007, Vol. 22, No. 2, pp. 59–63. © Allerton Press, Inc., 2007. Original Russian Text © I.V. Korobko, M.V. Zinov’eva, E.P. Kopantsev, A.K. Allakhverdiev, I.B. Zborovskaya, E.D. Sverdlov, 2007, published in Molekulyarnaya Genetika, Mikro- biologiya i Virusologiya, 2007, No. 2, pp. 18–20. 59 c-Met is a receptor tyrosine protein kinase, the anomalous activation of which by hepatocyte growth factor (HGF) may lead to cell transformation and pro- mote the progression of various types of tumors, by directly influencing the proliferation, motility, and invasiveness of the cells [2, 4]. The expression of c-Met is specific for epithelial cells, whereas HGF is produced by cells of mesenchymal origin and acts in a paracrine manner, binding to a receptor on epithelial cells [5, 8]. Changes in the c-Met/HGF system are noted in tumors of various types and may be directly associated with their progression [2, 4, 10]. Anomalous activation of the protooncogene c-Met in tumor cells may occur according to various mechanisms, including mutations in c-Met that lead to its constitutive activation, an increase in the expression of c-Met, and anomalous expression of HGF by c-Met-positive tumor cells, which leads to autocrine activation of the receptor [2]. Finally, the expression of c-Met by tumor cells and HGF by the surrounding stromal fibroblasts may be changed on account of the influence of the tumor cells on the cells of the stroma and, conversely, may lead to an increase in the expression of components of the paracrine system, c-Met and HGF [1, 12]. The results of a number of studies suggest that the c-Met/HGF system may play a definite role in the pro- gression of lung tumors. The increase in the expression of c-Met and the level of immunoreactivity of HGF in non-small cell lung carcinomas are correlated with a poor prognosis for the development of the disease and a shortening of the patients' lifetimes [7, 11, 16, 17, 21]. The influence of the c-Met/HGF system on the develop- ment of tumors and their metastasis is also confirmed by the fact that its inhibition caused a suppression of the growth of lung tumors and their metastasis [8, 9, 19], and, on the contrary, an artificial activation of it as a result of the production of exogenous HGF led to an increase in spontaneous carcinogenesis in the lungs [20], growth and invasion of tumors [14]. In the inves- tigations of M. Olivero et al. [13], a comparative analy- sis of the expression of c-Met and HGF in non-small cell lung carcinomas and adjacent unchanged tissues, conducted using the Western blot method, revealed a frequent (25% of the cases) increase in the expression of c-Met, as well as increased expression of HGF. The expression of c-Met was often (75% of the cases) observed in adenocarcinomas and more rarely (39%) in squamous cell carcinoma [7]. The predominant Expression of c-Met and HGF in Non-Small Cell Lung Carcinomas I. V. Korobko a, b , M. V. Zinov’eva c , E. P. Kopantsev c , A. K. Allakhverdiev f , I. B. Zborovskaya e , and E. D. Sverdlov d a Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia b University of Oslo, Norway; Center for Medical Research in Russia, Moscow, Russia c Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia d Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia e Scientific Research Institute of Carcinogenesis of the Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia f Scientific Research Institute of Clinical Oncology of the Blokhin Russian Cancer Research Center, Moscow, Russia Received September 28, 2006 Abstract—Changes in the c-Met/HGF system are noted in tumors of various types and may be directly related to their progression. In particular, the c-Met/HGF system may play a definite role in the progression of lung tumors, and changes in the expression of c-Met and HGF may occur in non-small cell lung carcinomas. In this work we analyzed the change in the expression of c-Met and HGF in non-small cell lung carcinomas in com- parison with the adjacent normal tissue, using a semiquantitative PCR method. The results of the investigations revealed transcription of c-Met in 50% of the cases of squamous cell lung carcinoma and an increase in the number of transcripts in 2 tumors out of 25 analyzed (8%). Expression of HGF was established in only two cases of squamous cell carcinoma. At the same time, a transcript of c-Met was detected in all five investigated samples of lung adenocarcinomas; an increase in the level of the c-Met transcript was observed in three cases in comparison with that in the adjacent unchanged tissues, whereas a HGF transcript was determined in two cases of lung adenocarcinomas. Thus, the expression of c-Met, but not of HGF, is often observed in non-small cell lung carcinomas, especially in adenocarcinomas, and, in agreement with the results of previous investiga- tions, can serve as an indicator of an aggressive course and progression of non-small cell lung carcinomas. DOI: 10.3103/S0891416807020048