Man Lung Transforming Growth Factor Alpha

Human bronchial carcinomas were studied for the presence, distribution, ultramicroscopic localization and transcription of the Transforming Growth Factor a (TGFα). Using radioimmunoassay, TGFα was detected in 11 of 12 bronchial carcinoma tissues, histologically 9 cases of squamous cell carcinoma and 3 cases adenocarcinoma. The level of TGFα was from 0.26ng to 1.26ng per gram tissue. There was no significant difference of TGFα level between the two types of carcinoma. TGFα was not detectable in one squamous cell carcinoma and probably caused by a too small sample of tissue or no production of TGFα in tumor tissue of this case. TGFα was not detectable in the patient's serum with bronchial carcinoma before and after operation, normal serum and normal lung tissues. Immunohistochemical stain of 52 cases of bronchial carcinoma was carried out by PAP method. From the results of observation, all the 18 cases of adenocarcinoma tissues showed positive immunoreaction to TGFα. The TGFα positive granules were found in nearly every tumor cell in each section. But only 23 of 26 squamous cell carcinomas showed positive reaction to TGFα. Another 3 cases showed negative reaction. The TGFα positive granules were found in vast majority of tumor cells in 16 cases and in part or even a few tumor cells in 7 cases. There was no distinct TGFα positive granules could be found in both adcno— and squamous carcinoma interstitial tissues. TGFα positive granules was not found in all the 8 cases of small cell carcinoma. The genetic information may be important in determing the various expression of TGFα in bronchial carcinoma. In addition, possible TGFα positive granules were found in the embryonic lung and liver tissues. Normal lung tissues and some atypical hyperplasia tissues showed negative reaction to TGFα. The ultrastructural localization of TGFα in the bronchial carcinoma cells was observed by using electron immunohistochemistry. TGFα was found to exist in two forms in the cytoplasm: free TGFα and TGFα in capsula. The latter may be the storage form of TGFα. TGFα was found in the tumor cell membrane too. The TGFα in membrane was inferred to have bound to its functional receptor. These results of observation provided morphological evidences to support the tumor autocrine theory for the first time. Finally, utilizing a radiolabeled TGFα cDNA in dotting hybridization, all the 6 cases of bronchial carcinoma tested were determined to contain TGFα-mRNA. These findings suggested that bronchial carcinoma express TGFα gene and the TGFα protein was produced by tumor cells themselves. TGFα is one of the typical autocrine growth factors and plan an important role in the development of bronchial carcinoma. The relationship between TGFα and bronchial carcinoma was discussed boradly and the possible application of TGFα was commanded.