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转化生长因子的旁分泌作用

Paracrine action of transforming growth factors.

作者信息

Gol-Winkler R

出版信息

Clin Endocrinol Metab. 1986 Feb;15(1):99-115. doi: 10.1016/s0300-595x(86)80044-5.

DOI:10.1016/s0300-595x(86)80044-5
PMID:3006950
Abstract

Polypeptide growth factors form a class of regulatory molecules which exert their effects by binding to specific receptors present on the cell surface. Most of the time the exact role of these factors in the healthy body is unknown. Some, like PDGF and TGF beta, seem to be involved in wound healing. Others, like EGF, promote epithelial cell growth and differentiation. The site of synthesis of most polypeptide growth factors is unknown. Their target can be identified by detecting the cells which present the specific receptors at their surface. It is though that polypeptide growth factors have a paracrine mode of action. Many different cancerous cells produce polypeptide growth factors and the appropriate receptors. Thus, they are able to stimulate their own growth in an autocrine fashion. Recently, some polypeptide growth factors and receptor genes or cDNAs have been molecularly cloned. Growth factor genes and messengers are much more complex than would be expected from the size of the polypeptide. Some cDNAs have been introduced into bacterial expression vectors and large amounts of the factors have been produced by bacteria. New tools, such as molecular probes and specific antibodies, are thus now available to investigate the production of the growth factors and their receptors. The same tools will facilitate the identification and understanding of the molecular mechanism whereby cancerous cells produce the growth factors and the appropriate receptors simultaneously. The importance of growth factors and receptors in cancer is stressed by the finding that three oncogenes are in fact the genes coding for one growth factor and two receptors. Finally, the molecular probes and the specific antibodies raised against these molecules can be used to identify precisely the growth factor(s) and receptor(s) produced abnormally in cancers. Antibodies that inhibit specifically the interaction of this very growth factor with its receptor could then be developed, thus allowing human tumour cell growth to be controlled.

摘要

多肽生长因子构成一类调节分子,它们通过与细胞表面存在的特定受体结合来发挥作用。大多数情况下,这些因子在健康机体中的确切作用尚不清楚。有些因子,如血小板衍生生长因子(PDGF)和转化生长因子β(TGFβ),似乎参与伤口愈合。其他一些因子,如表皮生长因子(EGF),则促进上皮细胞的生长和分化。大多数多肽生长因子的合成部位尚不清楚。它们的靶细胞可通过检测表面呈现特定受体的细胞来确定。据认为,多肽生长因子具有旁分泌作用模式。许多不同的癌细胞会产生多肽生长因子和相应的受体。因此,它们能够以自分泌方式刺激自身生长。最近,一些多肽生长因子及其受体基因或cDNA已被分子克隆。生长因子基因和信使比根据多肽大小所预期的要复杂得多。一些cDNA已被引入细菌表达载体,细菌已大量生产这些因子。因此,现在有了新的工具,如分子探针和特异性抗体,可用于研究生长因子及其受体的产生。同样的工具将有助于识别和理解癌细胞同时产生生长因子和相应受体的分子机制。发现三个癌基因实际上是编码一种生长因子和两种受体的基因,这突出了生长因子和受体在癌症中的重要性。最后,针对这些分子产生的分子探针和特异性抗体可用于精确鉴定癌症中异常产生的生长因子和受体。然后可以开发能特异性抑制这种生长因子与其受体相互作用的抗体,从而控制人类肿瘤细胞的生长。

相似文献

1
Paracrine action of transforming growth factors.转化生长因子的旁分泌作用
Clin Endocrinol Metab. 1986 Feb;15(1):99-115. doi: 10.1016/s0300-595x(86)80044-5.
2
Growth factors and cancer.生长因子与癌症
Cancer Res. 1986 Mar;46(3):1015-29.
3
[Growth factors. A new dimension in understanding oncogenesis].
Klin Wochenschr. 1985 Aug 16;63(16):740-6. doi: 10.1007/BF01733825.
4
Growth factors and oncogenes in human malignant glioma.人类恶性胶质瘤中的生长因子与癌基因
Neurol Clin. 1985 Nov;3(4):785-99.
5
Transformation-related growth factors and their receptors.转化相关生长因子及其受体。
Int J Cell Cloning. 1986 Jul;4(4):224-36. doi: 10.1002/stem.5530040401.
6
8th San Antonio Breast Cancer Symposium--Plenary lecture. Autocrine and paracrine growth regulation of human breast cancer.第八届圣安东尼奥乳腺癌研讨会——全会演讲。人类乳腺癌的自分泌和旁分泌生长调节。
Breast Cancer Res Treat. 1986;7(2):59-70. doi: 10.1007/BF01806790.
7
Polypeptide growth factors: roles in normal and abnormal cell growth.多肽生长因子:在正常和异常细胞生长中的作用。
Annu Rev Cell Biol. 1987;3:443-92. doi: 10.1146/annurev.cb.03.110187.002303.
8
Growth factors and oncogenes in human gastrointestinal carcinomas.人类胃肠道癌中的生长因子与癌基因
J Cancer Res Clin Oncol. 1990;116(2):121-31. doi: 10.1007/BF01612665.
9
Polypeptide growth factors in the regulation of human tumor cell proliferation.多肽生长因子在人类肿瘤细胞增殖调控中的作用
Curr Opin Oncol. 1991 Feb;3(1):70-4. doi: 10.1097/00001622-199102000-00011.
10
Tumor secretion of growth factors.肿瘤生长因子的分泌
Endocrinol Metab Clin North Am. 1991 Sep;20(3):539-63.

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Bacterial modulins: a novel class of virulence factors which cause host tissue pathology by inducing cytokine synthesis.细菌调节素:一类新型毒力因子,通过诱导细胞因子合成导致宿主组织病理变化。
Microbiol Rev. 1996 Jun;60(2):316-41. doi: 10.1128/mr.60.2.316-341.1996.
2
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Cancer Metastasis Rev. 1987;5(3):205-50. doi: 10.1007/BF00046999.