Cooperativity of Nkx3.1 and Pten loss of function in a mouse model of prostate carcinogenesis

MJ Kim, RD Cardiff, N Desai… - Proceedings of the …, 2002 - National Acad Sciences
MJ Kim, RD Cardiff, N Desai, WA Banach-Petrosky, R Parsons, MM Shen, C Abate-Shen
Proceedings of the National Academy of Sciences, 2002National Acad Sciences
Mouse models have provided significant insights into the molecular mechanisms of tumor
suppressor gene function. Here we use mouse models of prostate carcinogenesis to
demonstrate that the Nkx3. 1 homeobox gene undergoes epigenetic inactivation through
loss of protein expression. Loss of function of Nkx3. 1 in mice cooperates with loss of
function of the Pten tumor suppressor gene in cancer progression. This cooperativity results
in the synergistic activation of Akt (protein kinase B), a key modulator of cell growth and …
Mouse models have provided significant insights into the molecular mechanisms of tumor suppressor gene function. Here we use mouse models of prostate carcinogenesis to demonstrate that the Nkx3.1 homeobox gene undergoes epigenetic inactivation through loss of protein expression. Loss of function of Nkx3.1 in mice cooperates with loss of function of the Pten tumor suppressor gene in cancer progression. This cooperativity results in the synergistic activation of Akt (protein kinase B), a key modulator of cell growth and survival. Our findings underscore the significance of interactions between tissue-specific regulators such as Nkx3.1 and broad-spectrum tumor suppressors such as Pten in contributing to the distinct phenotypes of different cancers.
National Acad Sciences