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.

[1]  Michael C. Ostrowski,et al.  ras oncogene activation of a VL30 transcriptional element is linked to transformation. , 1990, Molecular and cellular biology.

[2]  G. Smith,et al.  Cytogenetic profile of in vitro spontaneously transformed and chemical tumor-derived cell lines related to the mouse lung alveologenic carcinoma. , 1990, Cancer research.

[3]  C. Marshall,et al.  Stimulation of phosphatidylcholine hydrolysis, diacylglycerol release, and arachidonic acid production by oncogenic ras is a consequence of protein kinase C activation. , 1989, The Journal of biological chemistry.

[4]  G. Smith,et al.  Cloned murine non-malignant, spontaneously transformed and chemical tumour-derived cell lines related to the type 2 pneumocyte. , 1989, Cell biology international reports.

[5]  G. C. Rhodes,et al.  Enhanced malignant phenotype of urethane-induced lung adenoma associated with sialoadenectomy in BALB/c mice. , 1989, Carcinogenesis.

[6]  G. Smith,et al.  Expression of fibronectin on clonally related transformed and control sublines from an epithelial cell strain and a tumor line of mouse alveolus. , 1988, Cancer research.

[7]  I. Pastan,et al.  Molecular evidence for the lack of epidermal growth factor receptor gene expression in small cell lung carcinoma cells. , 1987, Cancer research.

[8]  G. Smith,et al.  Malignant epithelial cell strains cultured from BALB/c mouse lung adenoma. , 1987, Cell biology international reports.

[9]  H. Kleinman,et al.  The control of DNA synthesis in primary cultures of hepatocytes from adult and young rats: Interactions of extracellular matrix components, epidermal growth factor, and the cell cycle , 1987, Journal of cellular physiology.

[10]  E. Rozengurt.  Early signals in the mitogenic response. , 1986, Science.

[11]  L. King,et al.  Role of epidermal growth factor in carcinogenesis. , 1986, Cancer research.

[12]  G. Smith,et al.  Onset of neoplastic phenotype in an epithelial cell strain from adult BALB/c mouse lung alveolus. , 1986, Journal of the National Cancer Institute.

[13]  H. Kurachi,et al.  Evidence for the involvement of the submandibular gland epidermal growth factor in mouse mammary tumorigenesis. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[14]  G. Smith,et al.  Establishment of epithelial cell strains from normal adult mouse lung resembling a urethane-induced lung adenoma cell strain and a metastasizing mouse lung carcinoma cell line. , 1984, Cell biology international reports.

[15]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[16]  R. Hynes,et al.  Three different fibronectin mRNAs arise by alternative splicing within the coding region , 1983, Cell.

[17]  R G Duggleby,et al.  A nonlinear regression program for small computers. , 1981, Analytical biochemistry.

[18]  T. Chen,et al.  In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. , 1977, Experimental cell research.

[19]  M. Young,et al.  Tumor growth: suppression in mice by submanidibular gland extirpation. , 1975, Journal of the National Cancer Institute.