- 作者: June L. Traicoff Sumudra Periyasamy Michael G. Brattain William Grady Graham Casey
- 作者服務機構: Department of Molecular Biology and Microbiology, Case Western Reserve University, Ireland Cancer Center, University Hospitals of Cleveland, and Department of Cancer Biology, Lermer Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Biochermistry and Molecular Biology, Medical College of Ohio, Toledo, Ohio; Roswell Park Cancer Institute, Buffalo, N,Y., USA
- 中文摘要: --
- 英文摘要:
We characterized the mechanism of transforming
growth factor beta (TGF-β) resistance in the VACO-411
human colon carcinoma line. VACO-411 is unique for
several reasons, including having a novel mutator phe-
notype and wild-type p53. Like many colon tumors,
VACO-411 is not growth inhibited by TGF-β. However,
VACO-411 represents a subset of colon tumors that are
resistant to TGF-β-mediated growth inhibition, despite
the expression of functional TGF-β receptors. VACO-411
expresses cell surface TGF-β receptor types I and II, and
the coding regions of these receptors are wild type. To
further characterize the nature of the VACO-411 defect,
we fused VACO-411 with the human breast carcinoma
line MCF-7. MCF-7 is also resistant to TGF-p-mediated
growth inhibition. However, unlike VACO-411, MCF-7
lacks cell surface expression of TGF-P receptor type II,
but does contain an intact postreceptor signaling path-
way, as shown by regeneration of TGF-P sensitivity fol-
lowing wild-type TGF-P receptor type II transfection. In
contrast to parental VACO-411 and MCF-7, the morpho-
logically distinct cell hybrids were growth inhibited by
TGF-β. Therefore, the TGF-P defect in VACO-411 is a
postreceptor, loss-of-function mutation which can be ge-
netically complemented. The data suggest that the
VACO-411 defect in TGF-β signaling will be able to be
further complemented by microcell-mediated chromo-
some transfer. - 中文關鍵字: --
- 英文關鍵字: Transforming growth factor beta. Signal transduction. Cell fusions. Complementation. Colon