TRANSFORMING GROWTH FACTORS FROM HUMAN MAMMARY TISSUES

转化人类乳腺组织的生长因子

• 批准号: 4691883
• 负责人: D S SALOMON
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4691883
• 关键词: breast neoplasms; clone cells; deficient growth media; electrofocusing; epidermal growth factor; fibroblasts; gene expression; growth factor; growth media; high performance liquid chromatography; human milk; human tissue; mammary epithelium; molecular weight; oncogenes; transforming growth factors

The presence and role of transforming growth factors (TGFs) in human mammary carcinoma cells is being defined. Alpha-TGFs resemble epidermal growth factor (EGF) in that they are able to compete with EGF mouse and human EGF but fail to cross-react with antibodies generated against these two species of EGF. Alpha-TGFs can be recovered from the acid-treated, concentrated conditioned medium (CM) of a human mammary carcinoma cell line, MCF-7, and ten individual clones derived from this cell line. The level of TGF activity associated with the CM varied amongst the different MCF-7 clones and showed no correlation with either the number of EGF receptors expressed on these cells or with the intrinsic ability of these clones to grow in soft agar as colonies. The TGF in the CM is an acid heat stable peptide whose activity is destroyed by reduction. It has a molecular weight of approximately 6000 and a pI of 4.0 TGF activity can also be detected in the crude, acid-ethanol extracts prepared from MCF-7 cells propagated as tumors in nude mice, in the acid-ethanol extracts obtained from two transplantable human mammary adenocarcinomas, Clouser I and II, and in 3 out of 4 primary human breast carcinoma samples. Relatively high levels of TGF activity can be found in crude, delipidated, decaseinated human milk obtained from at least 30 individual donors. The levels of TGF in the milk samples vary from individual donors and are generally highest in clostrum. Following isoelectric focusing (IEF), three distinct TGF species can be detected in the human breast tumor samples with identical species found in human milk. The TGF with a pI of 3.8 - 4.0, mammary-derived growth factor-II (MDGF-II), has been purified approximately 10,000-fold. This alpha-TGF species is virtually identical to the species found in the CM from MCF-7 cells. This acidic alpha-TGF is biologically and physiochemically distinct from the major species of human EGF in milk.

转化生长因子（TGF）在人乳腺癌中的存在及其作用 乳腺癌细胞正在定义中。 α-TGF类似于表皮 EGF生长因子（EGF），因为它们能够与EGF小鼠竞争， 但不能与针对这些抗体产生抗体交叉反应 两种EGF α-TGF可以从酸处理的， 人乳腺癌细胞的浓缩条件培养基（CM） 细胞系MCF-7和源自该细胞系的10个单独克隆。 的 与CM相关的TGF活性水平在不同的 MCF-7克隆的数量与EGF的数量无关， 这些细胞上表达的受体或这些受体的内在能力， 克隆在软琼脂中生长为菌落。 CM中的TGF是一种酸性热 活性被还原破坏的稳定肽。 它有一个 分子量约6000和pI为4.0的TGF活性可 也可在MCF-7制备的粗酸乙醇提取物中检测到 细胞在裸鼠中作为肿瘤增殖，在酸-乙醇提取物中 从两个可移植的人乳腺腺癌，Clouser I 和II，并且在4个原发性人乳腺癌样品中的3个中。 相对高水平的TGF活性可以在粗的、脱脂的、 从至少30名个体捐赠者处获得的去酪蛋白人乳。 的 乳汁样品中TGF的水平因个体供体而异， 通常在倒卵座最高。 在等电聚焦（IEF）之后，三个 在人乳腺肿瘤样品中可以检测到不同的TGF种类， 在母乳中发现的相同物种。 pI为3.8 - 4.0的TGF， 乳腺源性生长因子-II（MDGF-II），已被纯化约 一万倍 这种α-TGF种类实际上与 在MCF-7细胞的CM中发现。 这种酸性α-TGF在生物学上是 并且在物理化学上不同于牛奶中的主要人类EGF种类。