Regulation of Lewis lung carcinoma invasion and metastasis by protein kinase A

Int J Cancer. 1995 Mar 29;61(1):104-9. doi: 10.1002/ijc.2910610118.


Metastatic Lewis lung carcinoma (LLC-LN7) cells have increased protein kinase A (PKA) activity and are more invasive in vitro than are non-metastatic (LLC-C8) cells. To determine whether PKA mediates the in vitro invasiveness and in vivo metastatic capabilities of these tumor cells, the LLC variants were stably transfected to over-express the C alpha subunit of PKA, and thus to have increased PKA activity, or to express a mutant cAMP-resistant PKA R1 alpha subunit which blocks PKA activation. Wild-type LLC-LN7 tumor cells were invasive in vitro and in vivo, recurred after tumor excision and metastasized to the lungs. However, they lost these properties after transfection to express the mutant R1 alpha that blocks PKA activation. The non-invasive, non-recurring and non-metastatic LLC-C8 cells gained the capacity to invade, to recur following tumor excision and to metastasize when transfected to express the PKA C alpha subunit.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Basement Membrane / enzymology
  • Basement Membrane / pathology
  • Carcinoma, Lewis Lung / enzymology*
  • Carcinoma, Lewis Lung / pathology*
  • Carcinoma, Lewis Lung / secondary
  • Cell Movement / physiology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Enzyme Activation
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / secondary
  • Macromolecular Substances
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / enzymology
  • Neoplasm Recurrence, Local / pathology
  • Transfection


  • Macromolecular Substances
  • Cyclic AMP-Dependent Protein Kinases