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Role of receptor complexes in resistance or sensitivity to growth inhibition by TGFβ in intestinal epithelial cell clones
Author(s) -
Mulder Kathleen M.,
Segarini Patricia R.,
Morris Sheila L.,
Ziman Jill M.,
Choi Ho Gene
Publication year - 1993
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041540120
Subject(s) - receptor , transforming growth factor , autocrine signalling , biology , clone (java method) , microbiology and biotechnology , cell growth , cell culture , endocrinology , medicine , biochemistry , gene , genetics
Abstract Untransformed rat intestinal epithelial cells (IEC‐18) were chemically mutagenized, selected in the presence of TGFβ 1 , and cloned by limiting dilution. Two clones (4–5, 4–6) were resistant to growth inhibition by both TGFβ 1 and TGFβ 2 . Another clone (4–1) was more sensitive to both TGFβ isoforms (relative to parental IEC‐18 cells). IC 50 values for TGFβ 1 and 2 in the 4–1 cells were at least 1/9 those of the parental cells; growth rates were reduced by 49% for TGFβ 1 and by 26% for TGFβ 2 in this clone. This increased sensitivity to TGFβ was explained by the 5‐ to 10‐fold increase, relative to parental cells, in binding of TGFβ 1 and TGFβ 2 to both the type I and II receptors. In contrast, the resistance to growth inhibition by TGFβ in the 4–5 and 4–6 cells could not be explained by a decrease in either TGFβ binding affinities or in total number of receptors expressed, by the presence of serum binding components, or by occupation of receptor binding sites with autocrine TGF‐β 1 . However, in comparison to TGFβ‐sensitive cells (IEC‐18, 4–1), the resistant cells displayed a higher ratio of type II relative to type I receptor binding by TGF‐β 1 . Thus, a critical ratio of binding to receptor subtypes correlated with growth inhibition by TGF‐β 1 . Resistance to TGF‐β 2 in the same clones did not appear to be receptor related. Thus different mechanisms for resistance to TGF‐β 1 and TGF‐β 2 were observed within a given clone. © 1993 Wiley‐Liss, Inc.