The link between apoptosis and malignant cell growth is firmly established, and various forms of
therapy in
cancer, e.g., the use of
DNA-damaging chemotherapeutic drugs, are based on the principle of inducing apoptosis in malignant cells. However, in many known instances,
tumor cells develop resistance to apoptosis through various mechanisms. Thus, interventions designed to facilitate
tumor cells apoptosis are likely to have a therapeutic benefit. PKCtheta, which is expressed relatively selectively in T cells, plays an important role in mature T cell activation and proliferation upon its translocation to the plasma membrane. PKCtheta is necessary for induction of the
interleukin-2 (IL-2) gene because the
transcription factors AP-1 and
NF-kappaB, which are essential for
IL-2 gene promoter activation, are main targets of PKCtheta. Recent studies revealed that PKCtheta provides an important survival signal that protects leukemic T cells from Fas- or UV-induced apoptosis. These findings and the constitutive localization of PKCq in the membrane of some leukemic T cells suggests that it plays a role in leukemic T cell survival and/or proliferation, and that selective PKCtheta-inhibitory strategies may facilitate elimination of malignant T cells. The high-affinity
IL-2 receptor (IL-2Ralpha) is a major target of receptor-directed
therapy in several human diseases, and it is constitutively expressed by the malignant cells in some
T cell leukemias, suggesting an autocrine IL-2/IL-2R loop that participates in the expansion of leukemic IL-2R(+) cells. Therefore, given the essential role of PKCtheta in
IL-2 production,
IL-2 gene regulation by PKCtheta could also be of therapeutic interest.