8th San Antonio Breast Cancer Symposium--Plenary lecture. Autocrine and paracrine growth regulation of human breast cancer.
We consider the hypothesis that estrogen control of hormone dependent breast cancer is mediated by autocrine and paracrine growth factors secreted by the breast cancer cells themselves. Though we show direct, unmediated effects of estrogen on specific cell functions, we also provide evidence that human breast cancer cells secrete a collection of growth factors (IGF-I, TGF alpha, TGF beta, a PDGF-like competency factor, and at least one new epithelial colony stimulating factor). Some of these are estrogen-regulated in hormone dependent cells, and are constitutively increased in cells which acquire independence either spontaneously or by ras transfection. Collectively, the secreted growth factors are capable of promoting tumor formation by MCF-7 cells in nude mice, though not to the same extent as estrogens. There would seem to be potential for clinical intervention in the autocrine and paracrine control of breast cancer cells, including some cells which are no longer dependent on estrogens.
D001943:Breast Neoplasms / Q000503:physiopathology*; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004815:Epidermal Growth Factor / Q000502:physiology; D004848:Epithelium / Q000503:physiopathology; D066246:ErbB Receptors; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D009361:Neoplasm Invasiveness; D009930:Organic Chemicals; D010455:Peptides / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D011960:Receptors, Estrogen / Q000502:physiology; D015291:Transforming Growth Factors; D014410:Tumor Stem Cell Assay
D004967:Estrogens; D006133:Growth Substances; D009930:Organic Chemicals; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; C042320:colony promoting activity; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D015291:Transforming Growth Factors; D066246:ErbB Receptors