Abstract
Gα12, the α-subunit of G protein G12, is ubiquitously expressed and it has been identified as a putative “causative oncogene” of soft-tissue sarcomas. Overexpression of wild-type or GTPase-deficient mutant of Gα12 (Gα12Q229L or Gα12QL) leads to the oncogenic transformation of NIH3T3 cells. Gα12QL-tramsformed NIH3T3 cells show a distinct oncogenic phenotype defined by increased cell proliferation, anchorage-independent growth, reduced growth-factor dependency, attenuation of apoptotic signals, and neoplastic cytoskeletal changes. In this study, the genes contributing to the reduced growth-factor dependency of Gα12QL-NIH3T3 cells were identified by transcription profiling of serum-starved Gα12QL-transformed NIH3T3 (Gα12QL-NIH3T3) cells. Results from these studies indicate that Gα12QL stimulates the expression of genes that promote cell growth. The increased expressions of growth-promoting genes in Gα12QL-NIH3T3 cells were validated by semiquantitative reverse transcription-polymerase chain reaction and immunoblot analyses. Further studies aimed at investigating the critical role of two of such upregulated genes, namely PDGFRα and JAK3, indicated that the inhibition of PDGFRα or JAK3 activity-attenuated Gα12QL-mediated serum-independent cell proliferation. These studies point to possible novel autocrine and/or paracrine control mechanisms involving PDGFRα and JAK3 in Gα12-mediated proliferation and oncogenesis.
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Kumar, R.N., Radhika, V., Audigé, V. et al. Proliferation-specific genes activated by Gα12 . Cell Biochem Biophys 41, 63–73 (2004). https://doi.org/10.1385/CBB:41:1:063
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DOI: https://doi.org/10.1385/CBB:41:1:063