Peters G, Brookes S, Smith R, Placzek M, Dickson C
Imperial Cancer Research Fund Laboratories, St. Bartholomews Hospital, London, United Kingdom.
Proc Natl Acad Sci U S A. 1989 Aug;86(15):5678-82. doi: 10.1073/pnas.86.15.5678.
The fibroblast growth factor-related protooncogenes, int-2 and hst/k-FGF, are within 17 kilobase pairs of one another on mouse chromosome 7 and are in the same transcriptional orientation. Approximately 70% of tumors induced in BR6 mice by mouse mammary tumor virus have proviral insertions adjacent to the int-2 gene. We find that the murine homolog of the hst/k-FGF gene can also be transcriptionally activated by the insertion of mouse mammary tumor virus DNA either upstream or downstream of the gene. In most tumors, only one of these adjacent genes is activated, but in some cases both genes are expressed. One of the hst-expressing tumors also has a virally activated int-3 gene. At least five distinct cellular genes (int-1, -2, -3, -4, and hst/k-FGF) can therefore contribute, either singly or in concert, to the development of histologically indistinguishable mammary tumors in mice infected by mouse mammary tumor virus.
成纤维细胞生长因子相关原癌基因int-2和hst/k-FGF在小鼠7号染色体上彼此相距17千碱基对以内,且转录方向相同。约70%由小鼠乳腺肿瘤病毒在BR6小鼠中诱导产生的肿瘤,其前病毒插入位点紧邻int-2基因。我们发现,hst/k-FGF基因的小鼠同源基因也可通过小鼠乳腺肿瘤病毒DNA插入该基因的上游或下游而被转录激活。在大多数肿瘤中,这些相邻基因中只有一个被激活,但在某些情况下两个基因都会表达。一个表达hst的肿瘤还具有一个病毒激活的int-3基因。因此,至少五个不同的细胞基因(int-1、-2、-3、-4和hst/k-FGF)可单独或共同促成受小鼠乳腺肿瘤病毒感染的小鼠中组织学上无法区分的乳腺肿瘤的发生。