Suppressor genes for malignant and anchorage-independent phenotypes located on human chromosome 9 have no dosage effects.

M Q Islam, K Islam
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引用次数: 6

Abstract

We have previously shown that microcell-mediated transfer of a der(9)t(X;9) human chromosome (HSA), derived from human fibroblast strain GM0705, into the Syrian hamster cell line BHK-191-5C produced only near-tetraploid hybrids, although the recipient cell line contained a 1:1 ratio of near-diploid and near-tetraploid cells. However, the tumorigenicity and the anchorage independence could be suppressed in the near-tetraploid hybrids with one copy of the der(9)t(X;9) chromosome. The introduction of an HSA X chromosome did not suppress either of these phenotypes. We concluded that in addition to two suppressor genes, one for tumorigenicity and another for anchorage independence, HSA 9 might carry a third gene capable of inhibiting cellular growth in vitro, which had dosage effects. In the present study, keeping one copy of the der(9)t(X;9) chromosome, we have increased the hamster background chromosome number beyond hexaploid level by fusing two microcell-generated hybrid cell lines, where both malignant and anchorage-independent phenotypes were suppressed, with the parental malignant BHK-191-5C cell line. Tests with nude mice showed that hybrids containing one copy of the der(9)t(X;9) chromosome against the increased background of chromosomes of malignant parental origin were still suppressed for both phenotypes. These results suggest that the suppressor genes for malignancy and for anchorage independence have no dosage effects, in contrast to the suppressor gene(s) for cellular growth.

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位于人类第9号染色体上的恶性和非锚定表型的抑制基因没有剂量效应。
我们之前已经证明,将源自人成纤维细胞株GM0705的der(9)t(X;9)人染色体(HSA)微细胞介导转移到叙利亚仓鼠细胞系BHK-191-5C中只产生近四倍体杂种,尽管受体细胞系含有1:1比例的近二倍体和近四倍体细胞。然而,具有1个der(9)t(X;9)染色体拷贝的近四倍体杂种的致瘤性和锚定独立性可以被抑制。引入HSA X染色体并没有抑制这两种表型。我们得出结论,除了两个抑制基因,一个是致瘤性的,另一个是锚定独立性的,HSA 9可能携带第三个基因,能够在体外抑制细胞生长,具有剂量效应。在本研究中,我们保留一条der(9)t(X;9)染色体,通过将两个微细胞产生的杂交细胞系与亲本恶性BHK-191-5C细胞系融合,使仓鼠背景染色体数量超过六倍体水平,其中恶性表型和锚定非依赖性表型均受到抑制。用裸鼠进行的试验表明,在恶性亲本染色体背景增加的情况下,含有一个der(9)t(X;9)染色体拷贝的杂交后代在两种表型上仍然受到抑制。这些结果表明,与抑制细胞生长的基因相比,恶性肿瘤和锚定独立性的抑制基因没有剂量效应。
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