Chk2 mutation has been identified in several cancers including breast, colon, prostate, and lung cancers. Loss of the chk2 locus on chromosome 22q13 has been reported in breast, colorectal, ovarian, and brain tumors. Germ line mutations of chk2 have been found in Li-Fraumeni syndrome. Concomitant mutations in chk2 and TP53 have been observed in colon and breast cancer. The lake of FHIT Fragile Histidin Triad and disruption of the chk2 is detected in oral squamous carcinoma .FHIT is tumor suppressor gene that regulates chk2 phosphoralation in DNA damage pathway. Thus chk2 activation can be regulated by tumor suppressor genes. Chk2 inhibition enhance the level of mitosis in combination with either doxorubicin or cisplatin. Chk2-null mice increase survival when exposed to ionizing radiation. Chk2 knockout mice and chk2-defecient cells such as non small lung cancer are remarkably resistant to IR induced apoptosis and chemotherapy drugs. Low level or absent of chk2 kinase promote breast, prostate, thyroid, bladder, kidney, ovarian, and colorectal cancers. Epigenetic silencing of chk2 expression is shown in lung cancer. In addition; Chk2 siRNA prevented the release of the antiapoptotic factor survivin from the mitochondria, thus augmenting ionizing radiation (IR)- or doxorubicin-induced apoptosis. The chk2-specific inhibitor, VRX0466617 decreased IR-induced apoptosis whereas did not have the effect on the cytotoxicity of doxorubicin, taxol or cisplatin On the other hand, Chk2 knockout in colorectal cancer cells accelerate apoptosis.
Mir Mohammadrezaei F. The Role of chk2 in response to DNA damage in cancer cells[J]. Journal of Genetic Resources, 2015, 1(1): 31-34.