Changes in response to, and production of, transforming growth factor type beta during neoplastic progression in cultured rat tracheal epithelial cells.
As rat tracheal epithelial cells progress from a normal to a neoplastic phenotype there are systematic changes in their ability to produce and activate latent transforming growth factor type beta (TGF-beta) as well as systematic changes in their response to this growth factor. Using a TGF-beta radioreceptor binding competition assay it was found that normal proliferating rat tracheal cells in early primary culture produced latent TGF-beta. With the emergence of terminally differentiated cell populations active TGF-beta was also detected in the conditioned medium. When normal cells were cultured under conditions allowing for continued proliferation, no active TGF-beta was detected in the conditioned medium. Colonies of proliferating epithelial cells in 4-6 week primary cultures or subculturable tracheal cell lines did not produce detectable levels of active or latent growth factor. With neoplastic progression there was likewise a change in response to active TGF-beta. Normal tracheal cells in primary culture were highly sensitive to growth-factor-induced decreases in thymidine uptake as well as to the induction of terminal differentiation. Proliferating epithelial cells in late (4-6 week) primary cultures and preneoplastic, subculturable cell lines were often as sensitive as normal cells to the growth factor-induced decline in thymidine uptake. None of these altered populations, however, was induced to differentiate (to form cornified, cross-linked envelopes) in the presence of TGF-beta.
Terzaghi-Howe
M
M
Biology Division, Oak Ridge National Laboratory, TN 37831.
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004261:DNA Replication; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta; D013936:Thymidine / Q000378:metabolism; D014132:Trachea / Q000166:cytology* / Q000502:physiology; D015291:Transforming Growth Factors / Q000096:biosynthesis*
D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors; D013936:Thymidine