DNA-binding protein; Core component of the BAF (hSWI/SNF) complex. This ATP-dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation.
Tumorsuppressor
Loss-of-function of SMARCB1 in a liver cancer cell line (SKHep1) showed suppressed soft agar colony formation. In a xenograft model using stable SMARCB1 knockdown Huh7 cells tumors were reduced significantly after 40 days compared with control cells [1].
Homozygous knockout of the murine Smarcb1 results in early embryonic lethality [2,3], whereas heterozygous mice are born at the expected frequency and appear normal. However, beginning as early as 5 weeks of age, 8 heterozygous mice out of 125 mice develop tumors consistent with MRT (Malignant rhabdoid tumor). None of the 124 control mice developed tumors, as shown in [3]. In another study approximately 15% of heterozygous mice present with tumors, mostly undifferentiated or poorly differentiated sarcomas [2].
Utilizing a reversibly inactivating conditional allele, the loss of SmarcB1, results in highly penetrant cancer predisposition with 100% of mice developing mature CD8(+) T cell lymphoma or rare rhabdoid tumors with a median onset of only 11 weeks [4].
Die ursächliche Beteiligung an der Entstehung von Tumoren als Onkogen ist nicht gezeigt
[1] Hong, S. H. et al., Cancer Res, 2021, 81 (2), 356–370. doi: 10.1158/0008-5472.CAN-20-0568.
[2] Guidi, C. J. et al., Mol Cell Biol, 2001, 21 (10), 3598–3603. doi: 10.1128/MCB.21.10.3598-3603.2001.
[3] Roberts, C. W. et al., Proc Natl Acad Sci U S A, 2000, 97 (25), 13796–13800. doi: 10.1073/pnas.250492697.
[4] Roberts, C. W. M. et al., Cancer Cell, 2002, 2 (5), 415–425. doi: 10.1016/s1535-6108(02)00185-x.
