Yuan X J, McCarthy B D, Salgar S K, Kunz H W, Gill T J
Department of Pathology, University of Pittsburgh, School of Medicine, PA 15261, USA.
Am J Reprod Immunol. 1999 Jul;42(1):64-9. doi: 10.1111/j.1600-0897.1999.tb00467.x.
To study the mechanism of action of major histocompatibility complex (MHC)-linked genes affecting reproduction, growth, and susceptibility to chemical carcinogens.
Tumors derived from rat embryonic fibroblasts were transfected with cosmids from the Grc and its linked regions, the unrelated A region, and a nonMHC region, or with genes from the Grc, Grc-linked, and nonMHC regions, to determine whether they could suppress tumor growth as determined by in vitro (soft agar) and in vivo assays.
Tumor fibroblasts transfected with cosmids from the Grc or from the EC region decreased tumor growth in both the in vitro and in vivo assays. Transfection with individual genes from the Grc had no effect on tumor growth in either assay.
The effects of the Grc on reproduction, growth, and tumorigenesis are mediated by extended genetic effects, i.e., by the conformation of the DNA in this region. Similar effects were seen following transfection with cosmids from the Grc-linked EC region, and this finding strengthens the hypothesis that the conformation of the DNA in this general region is critical for its function. A similar effect has been described for the locus control region (LCR) in the beta-globin gene family in the human.
研究主要组织相容性复合体（MHC）相关基因对生殖、生长以及化学致癌物易感性的作用机制。
用来自Grc及其连锁区域、不相关的A区域和非MHC区域的黏粒，或来自Grc、Grc连锁区域和非MHC区域的基因转染源自大鼠胚胎成纤维细胞的肿瘤，通过体外（软琼脂）和体内试验来确定它们是否能抑制肿瘤生长。
用来自Grc或EC区域的黏粒转染的肿瘤成纤维细胞在体外和体内试验中均降低了肿瘤生长。用来自Grc的单个基因转染在两种试验中对肿瘤生长均无影响。
Grc对生殖、生长和肿瘤发生的影响是由扩展的遗传效应介导的，即由该区域DNA的构象介导。用来自与Grc连锁的EC区域的黏粒转染后也观察到类似效应，这一发现强化了这样的假说，即该一般区域DNA的构象对其功能至关重要。人类β-珠蛋白基因家族中的位点控制区（LCR）也有类似效应。
