DIFFERENTIAL EXPRESSION OF THE RETINOBLASTOMA GENE FAMILY MEMBERS IN LUNG CANCER

The retinoblastoma gene family is composed of three members: the retinoblastoma gene, one of the most well studied tumor suppressor genes and two related proteins, pi07 and Rb2/pl30. These three proteins share many structural and functional features and play a fundamental role in cell growth control. We evaluated, by immunocytochemical techniques, the expression of this family of proteins on 77 specimens, formalin fixed and paraffin embedded, obtained from patients with surgically resected lung cancer. Samples consisted of 39 squamous carcinomas, 12 adenocarcinomas, 9 bronchioloalveolar carcinomas, 6 small cell carcinomas, 9 carcinoids, 1 lymphoepitelioma, and 1 carcinosarcoma. The antibody used was: the anti-Rb monoclonal mouse xz77, and two polyclonal rabbit immune sera, ADL1 and ADL2, respectively against pRb2/pl30 and p 107. Experiments of im¬munoprécipitation and in vitro transcription translation were performed to verify the specificity of the antibodies against the retinoblastoma family proteins. This data were compared to the different histological grading (were provided) and to the expression of PCNA (the antibody used was monoclonal mouse anti-PCNA PC10). The investigated proteins displayed a different behavior when compared and contrasted to the different parameters. The highest percentage of undetectable expression levels in all the cases examined and the most tight inverse correlation with the histological grading and with PCNA expression was found for pRb2/pl30. This data could suggest an important role in the pathogenesis and progression of lung cancer of this protein. Presently, our lab is investigating the genetic structure and the protein expression of the Rb2/pl30 gene in several tumoral cell lines and lung cancer specimens, in order to possibly identify, spontaneously occurring, inactivating mutations.