Approaches to studying the role of growth factors in the progression of breast tumours from the steroid sensitive to insensitive state

R. J.B. King, D. Y. Wang, R. J. Daly, P. D. Darbre

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Progression from steroid sensitive to autonomous proliferation can be modelled in several cultured mammary tumour cell lines by long-term withdrawal of steroids. A feature of all the four systems studied thus far is that the basal growth in the absence of steroid increases with duration of steroid withdrawal until it reaches that obtained in the presence of steroid. It cannot be assumed that the increased proliferation in the absence of steroid is modulated by the same pathways as those stimulated by steroids in sensitive cells. Therefore, we feel that mechanisms of progression can best be studied via cell behaviour in the absence of steroid. With both the mouse S115 and human T-47-D systems, changes in sensitivity to several growth factors accompany progression; responses to TGFβ1 are of particular interest in the T-47-D cells where this growth factor becomes stimulatory in the steroid insensitive state. This is accompanied by upregulation of TGFβ1 mRNA. This upregulation of TGFβ agrees with the finding that ER - PR - primary human breast tumours contain more TGFβ1 than do ER+ PR+ tumours; TGFα has the opposite pattern. Furthermore, only 40 and 30 kDa TGFβ species have been detected within cultured cells and primary tumours; TGFα exists in a 30 kDa form. The functions of these large forms of TGFα and TGFβ are unclear. Our conclusions from these experiments is that the increased proliferation in the absence of steroid accompanying progression may not be mediated by the same pathways as those perturbed by steroids in sensitive cells. Furthermore, TGFβ1 may have different effects in steroid responsive and unresponsive cells.

Original languageEnglish
Pages (from-to)133-138
Number of pages6
JournalJournal of Steroid Biochemistry
Issue number1-6
Publication statusPublished - 1 Jan 1989
Externally publishedYes

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