Haas M, Mally M I, Bogenberger J M, Bogart M H, Buchanan M A, Augery-Bourget Y, Hyman R, Vogt M
EMBO J. 1986 Aug;5(8):1775-82. doi: 10.1002/j.1460-2075.1986.tb04426.x.
Primary tumors of X-ray-induced murine T cell lymphomas comprise autocrine, growth factor-dependent cells. We have grown cell lines from primary X-ray-induced thymic lymphomas (PXTLs) under conditions which minimize the progression of the cells from factor dependence to factor independence. All (22) PXTL lines grown secrete a growth factor which supports their own growth and which we will call lymphoma growth factor LGF. LGF-dependent cells are non-tumorigenic or poorly tumorigenic, do not clone in soft agar, have no detectable rearrangements in the c-myc or Pim-1 region and possess near diploid or pseudodiploid karyotypes without evidence for trisomy of chromosomes nos. 15 or 17. PXTL-secreted LGF has no interleukin 1, 2, or 3 activity nor do LGF-secreting cells synthesize detectable IL-1, -2, or -3 mRNA. LGF contains no detectable interferon or GM-CSF activity in specific bioassays. Purified EGF, TGF beta, and interleukin preparations are inactive on LGF-dependent PXTL cells. Thus LGF appears to be a new growth factor that is required for the proliferation of non-progressed T lymphoma cells. Upon progression PXTL cells become growth factor independent, are highly tumorigenic in vivo, clone in soft agar, and assume a near triploid karyotype containing numerous chromosomal aberrations. Thus in X-ray-induced lymphomagenesis an autocrine, LGF-dependent phase precedes the progressed phase characterized by rearrangements in the myc and/or Pim-1 regions as well as by many chromosomal aberrations visible in the karyotype.
X射线诱导的小鼠T细胞淋巴瘤的原发性肿瘤包含自分泌、生长因子依赖性细胞。我们在尽量减少细胞从因子依赖性向因子非依赖性进展的条件下，从原发性X射线诱导的胸腺淋巴瘤（PXTL）中培养出了细胞系。所有培养的22个PXTL细胞系均分泌一种生长因子，该因子支持其自身生长，我们将其称为淋巴瘤生长因子LGF。依赖LGF的细胞无致瘤性或致瘤性较差，不能在软琼脂中克隆，在c-myc或Pim-1区域无可检测到的重排，具有近二倍体或假二倍体核型，且无15号或17号染色体三体的证据。PXTL分泌的LGF无白细胞介素1、2或3活性，分泌LGF的细胞也不合成可检测到的IL-1、-2或-3 mRNA。在特定生物测定中，纯化的表皮生长因子（EGF）、转化生长因子β（TGFβ）和白细胞介素制剂对依赖LGF的PXTL细胞无活性。因此，LGF似乎是一种新的生长因子，是未进展的T淋巴瘤细胞增殖所必需的。PXTL细胞进展后变得不依赖生长因子，在体内具有高度致瘤性，能在软琼脂中克隆，并呈现出含有许多染色体畸变的近三倍体核型。因此，在X射线诱导的淋巴瘤发生过程中，一个自分泌、依赖LGF的阶段先于以myc和/或Pim-1区域重排以及核型中可见的许多染色体畸变特征的进展阶段。
