Disordered metabolism of microfilament proteins, tropomyosin and actin, in mouse mammary epithelial cells expressing the Ha-ras oncogene.
Synthesis of 37- and 41-kD tropomyosins (TM) is suppressed in fibroblasts expressing transforming oncogenes, which may contribute to the deranged microfilament structure seen in such cells (Cooper et al., Mol. Cell. Biol. 5, 972, 1985). To determine whether TM metabolism was also deranged when epithelial cells expressed a transforming oncogene, we studied cultured mouse mammary epithelial cells which express the activated c-Ha-ras oncogene either constitutively or through glucocorticoid activation of the oncogene linked to a mouse mammary tumor virus (MMTV) promoter. The epithelial cells expressed three major TM species, one at 37 kD and two at 35 kD, but lacked expression of a 41 kD TM typically found in fibroblasts. In oncogene-expressing cells synthesis of the 37 kD TM was not suppressed but synthesis of actin was increased 2-fold. Actin entered the cytoskeleton (CSK) normally, but TM accumulated in the CSK with a 50% reduction from normal in TM:actin ratio. Thus, in both epithelial cells and fibroblasts expressing transforming ras oncogenes, the metabolism of TM and actin is disordered so as to produce TM-deficient cytoskeletal structures which may be functionally or structurally defective. However, the result is achieved by different effects on metabolism of these proteins in the two cell types, suggesting that cellular responses to oncogene actions may be conditioned by the state of cell differentiation.
Bhattacharya
B
B
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland.
Ciardiello
F
F
Salomon
D S
DS
Cooper
H L
HL
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003599:Cytoskeleton / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007526:Isoelectric Point; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D014335:Tropomyosin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000199:Actins; D011518:Proto-Oncogene Proteins; D014335:Tropomyosin; D003907:Dexamethasone; D016283:Proto-Oncogene Proteins p21(ras)