Gustafson C E, Wilson P J, Lukeis R, Baker E, Woollatt E, Annab L, Hawke L, Barrett J C, Chenevix-Trench G
The Queensland Institute of Medical Research, The Bancroft Centre, Royal Brisbane Hospital Post Office, Australia.
Cancer Res. 1996 Nov 15;56(22):5238-45.
Chromosome 8p is considered, from loss of heterozygosity analysis, to be a strong candidate for the location of a tumor suppressor gene inactivated in colorectal cancer. We have found a 53% (27 of 51) rate of allelic loss at the LPL locus on 8p22, with the smallest region of overlap of deletions including the region D8S258 to D8S277. Using microcell-mediated monochromosome 8 transfer into three colorectal cancer cell lines, SW480, SW620 and HT29, we have demonstrated a reduction of tumorigenicity in SW620 hybrids. Partial deletions of chromosome 8 in some SW620/8 hybrids further delineate the critical region(s) to 8p22-23. Hybrids of the colorectal cancer cell lines SW480 and HT29 containing chromosome 8 did not show suppression of tumorigenesis, but the H29/8 hybrid showed total suppression of soft agar clonicity. This indicates an alternate pathway of mutational progression in these three lines, despite the fact that SW480 was derived from the same patient as SW620.
从杂合性缺失分析来看，8号染色体短臂（8p）被认为是在结直肠癌中失活的肿瘤抑制基因所在位置的有力候选区域。我们发现在8p22的脂蛋白脂肪酶（LPL）基因座上等位基因缺失率为53%（51个中有27个），缺失重叠的最小区域包括从D8S258到D8S277的区域。通过微细胞介导的8号单染色体转移到三种结直肠癌细胞系SW480、SW620和HT29中，我们证明了SW620杂交细胞系的致瘤性降低。一些SW620/8杂交细胞系中8号染色体的部分缺失进一步将关键区域划定到8p22 - 23。含有8号染色体的结直肠癌细胞系SW480和HT29的杂交细胞系未显示出肿瘤发生的抑制，但H29/8杂交细胞系显示出软琼脂克隆形成完全受到抑制。这表明尽管SW480与SW620来自同一患者，但这三种细胞系中存在突变进展的替代途径。
