EGF-receptor and extracellular matrix changes in mouse pulmonary carcinogenesis.
Malignant Balb/c mouse lung cell clones related to alveologenic carcinoma exhibited low levels of epidermal growth factor (EGF) receptor activity compared to nonmalignant cell clones. Immunoprecipitation of cell homogenates and immunohistochemistry on urethane-induced lung tumors suggest that the absence of activity reflects decreased amounts of EGF receptor protein. Low levels of EGF receptor alone cannot cause neoplastic transformation, since a nonneoplastic cell cone, B5D3, exhibited low levels of EGF receptor despite its nontransformed phenotype. The reduced levels of EGF receptor in malignant clones have been mimicked by long-term (12 h) treatment of a nontransformed cell clone with 200 nM phorbol dibutyrate. The detection of mutated ras oncogene in the transformed cell lines, taken together with the EGF receptor findings, suggests that more than one alteration in the signal transduction pathway may be necessary for transformation in alveologenic adenoma and carcinoma cell systems. A further phenotypic feature of transformation, reduced expression of the extracellular matrix proteins fibronectin and laminin, may be mediated at the transcriptional level.
Smith
G J
GJ
Carcinogenesis Research Unit, School of Pathology, University of New South Wales, Kensington, Australia.
Morris
C
C
Leigh
D
D
Rhodes
G C
GC
Wong
A
A
D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism*; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D007124:Immunoenzyme Techniques; D007457:Iodine Radioisotopes; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D011233:Precipitin Tests; D012334:RNA, Neoplasm / Q000032:analysis; D013363:Submandibular Gland / Q000502:physiology
D007457:Iodine Radioisotopes; D012334:RNA, Neoplasm; D066246:ErbB Receptors