Growth inhibition, enhancement of intercellular adhesion, and increased expression of carcinoembryonic antigen by overexpression of phosphoinositides-specific phospholipase C beta 1 in LS174T human colon adenocarcinoma cell line
- PMID: 10081486
- PMCID: PMC5921740
- DOI: 10.1111/j.1349-7006.1998.tb00522.x
Growth inhibition, enhancement of intercellular adhesion, and increased expression of carcinoembryonic antigen by overexpression of phosphoinositides-specific phospholipase C beta 1 in LS174T human colon adenocarcinoma cell line
Abstract
By using a retrovirus-derived system we generated derivatives of the human colon adenocarcinoma cell line LS174T (ATCC CL 188) that stably overexpress a full-length cDNA encoding the beta 1 isoform of bovine phosphoinositides-specific phospholipase C (PI-PLC). This was confirmed by the elevated levels of catalytic activity to release phosphoinositides from phosphatidylinositol (PI-PLC) or phosphatidylinositol-bis-phosphate (PIP2-PLC), and the enhanced expressions of messenger RNA and protein. PI-PLC beta 1 overexpresser clones grew to form cell clumps floating in liquid medium, whereas the pMV7-introduced control clones displayed morphologic characteristics that were very similar to those of the parent LS174T cell line. Three individual PI-PLC beta 1 overexpresser cell lines displayed increased doubling time (18.0 h, 21.5 h, and 23.8 h) when compared with 4 individual pMV7-introduced control cell lines (13.1 h, 10.7 h, 12.9 h, and 9.3 h). Anchorage-independent growth ability in soft agar medium was dramatically suppressed by overexpression of PLC beta 1, and the ability of PLC-overproducer clones to form aggregates when cultured in liquid medium was dramatically enhanced when compared with that of pMV7-introduced control clones. Tumorigenicity of PLC beta 1-overproducers was much weaker than that of vector-transduced control clones. The spontaneous release of carcinoembryonic antigen from PLC beta 1-overproducer clones was much higher than that from pMV7 control clones. The ability of PLC beta 1-overproducer clones to form aggregates during suspension culture was much stronger than that of the control clones. These results provide the first evidence that elevated levels of endogenous PI-PLC beta 1 suppress tumor cell growth, but enhance the ability to form cell aggregates and to release carcinoembryonic antigen, an intercellular adhesion molecule.
Similar articles
-
Release of carcinoembryonic antigen from human tumor cells by phosphatidylinositol-specific phospholipase C: highly effective extraction and upregulation from LS-174T colonic adenocarcinoma cells.Arch Biochem Biophys. 1993 Oct;306(1):125-32. doi: 10.1006/abbi.1993.1489. Arch Biochem Biophys. 1993. PMID: 8215392
-
Suppression of phospholipase C beta, gamma, and delta families alters cell growth and phosphatidylinositol 4,5-bisphosphate levels.Biochemistry. 1997 Dec 16;36(50):15949-58. doi: 10.1021/bi971721m. Biochemistry. 1997. PMID: 9398329
-
Overexpression of protein kinase C in HT29 colon cancer cells causes growth inhibition and tumor suppression.Mol Cell Biol. 1990 Sep;10(9):4650-7. doi: 10.1128/mcb.10.9.4650-4657.1990. Mol Cell Biol. 1990. PMID: 2388620 Free PMC article.
-
Nuclear phosphoinositide specific phospholipase C (PI-PLC)-beta 1: a central intermediary in nuclear lipid-dependent signal transduction.Histol Histopathol. 2005 Oct;20(4):1251-60. doi: 10.14670/HH-20.1251. Histol Histopathol. 2005. PMID: 16136505 Review.
-
[Phospholipase C inhibitor].Gan To Kagaku Ryoho. 1997 Sep;24(11):1611-7. Gan To Kagaku Ryoho. 1997. PMID: 9309162 Review. Japanese.
References
-
- ) Nishizuka , Y.Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C . Science , 258 , 607 – 614 ( 1992. ). - PubMed
-
- ) Berridge , M. J.Inositol triphosphate and calcium signaling . Nature , 361 , 315 – 325 ( 1993. ). - PubMed
-
- ) Rhee , S. G. and Choi , K. D.Regulation of inositol phospholipid‐specific phospholipase C isozymes . J. Biol. Chem. , 267 , 12393 – 12396 ( 1992. ). - PubMed
-
- ) Lee , C.‐W. , Park , D. J. , Lee , K.‐H. , Kim , C. G. and Rhee , S. G.Purification, molecular cloning, and sequencing of phospholipase C‐β4 . J. Biol. Chem. , 268 , 21318 – 21327 ( 1993. ). - PubMed
-
- ) Rhee , S. G. and Bae , Y. S.Regulation of phosphoinositide‐specific phospholipase C isozymes . J. Biol. Chem. , 272 , 15045 – 15048 ( 1997. ). - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous