Limits...
Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells.

Manthey C, Mern DS, Gutmann A, Zielinski AJ, Herz C, Lassmann S, Hasskarl J - BMC Cell Biol. (2010)

Bottom Line: ID1 protein is localized at the centrosomes and forced (over-)expression of ID1 results in errors during centrosome duplication.While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4.Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany.

ABSTRACT

Background: ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-)expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID1 have been detected in multiple human malignancies, and in some have been correlated with unfavorable clinical prognosis. ID1 protein is localized at the centrosomes and forced (over-)expression of ID1 results in errors during centrosome duplication.

Results: Here we analyzed the steady state expression levels of the four ID-proteins in 18 tumor cell lines and assessed the number of centrosome abnormalities. While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4. Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed.

Conclusions: This is the first report that shows that not only ectopic expression in tissue culture but endogenous levels of ID1 modulate centrosome numbers. Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness.

Show MeSH

Related in: MedlinePlus

Statistical data evaluation. A) Logarithmic ID1 expression data compared with number of centrosomal abnormalities; B) Spearman's rank correlation coefficient r looking at ID expression and centrosome abnormalities: r values above, p values below; r = 1 shows perfect correlation, r = 0 shows no correlation, 1> r > 0 shows positive correlation, in this case e.g. ID1 and centrosomal abnormalities.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2818612&req=5

Figure 4: Statistical data evaluation. A) Logarithmic ID1 expression data compared with number of centrosomal abnormalities; B) Spearman's rank correlation coefficient r looking at ID expression and centrosome abnormalities: r values above, p values below; r = 1 shows perfect correlation, r = 0 shows no correlation, 1> r > 0 shows positive correlation, in this case e.g. ID1 and centrosomal abnormalities.

Mentions: We have previously reported accumulation of supernumerary centrosomes in cells ectopically expressing ID1 [18,21]. No influence of ID2, ID3 or ID4 was detected then. Our findings here were very suggestive that endogenous ID1 expression might also influence centrosomal homeostasis in various cancer cell lines. Comparison of ID1 expression and the number of centrosomal abnormalities showed a clear and significant correlation of high ID1-expression with an increased number of centrosome abnormalities (Figure 4A) (Spearman's rank correlation coefficient p = 0.66804). Surprisingly, not only ID1 expression but also ID3 expression correlated with centrosome abnormalities (Spearman's coefficient p = 0.61976), whereas ID2 and ID4 did not. Similarly, colocalization of ID1 with centrosomes (i.e. with γ-tubulin) was more obvious in leukemic cells expressing higher levels of endogenous ID1 (Additional file 1).


Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells.

Manthey C, Mern DS, Gutmann A, Zielinski AJ, Herz C, Lassmann S, Hasskarl J - BMC Cell Biol. (2010)

Statistical data evaluation. A) Logarithmic ID1 expression data compared with number of centrosomal abnormalities; B) Spearman's rank correlation coefficient r looking at ID expression and centrosome abnormalities: r values above, p values below; r = 1 shows perfect correlation, r = 0 shows no correlation, 1> r > 0 shows positive correlation, in this case e.g. ID1 and centrosomal abnormalities.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2818612&req=5

Figure 4: Statistical data evaluation. A) Logarithmic ID1 expression data compared with number of centrosomal abnormalities; B) Spearman's rank correlation coefficient r looking at ID expression and centrosome abnormalities: r values above, p values below; r = 1 shows perfect correlation, r = 0 shows no correlation, 1> r > 0 shows positive correlation, in this case e.g. ID1 and centrosomal abnormalities.
Mentions: We have previously reported accumulation of supernumerary centrosomes in cells ectopically expressing ID1 [18,21]. No influence of ID2, ID3 or ID4 was detected then. Our findings here were very suggestive that endogenous ID1 expression might also influence centrosomal homeostasis in various cancer cell lines. Comparison of ID1 expression and the number of centrosomal abnormalities showed a clear and significant correlation of high ID1-expression with an increased number of centrosome abnormalities (Figure 4A) (Spearman's rank correlation coefficient p = 0.66804). Surprisingly, not only ID1 expression but also ID3 expression correlated with centrosome abnormalities (Spearman's coefficient p = 0.61976), whereas ID2 and ID4 did not. Similarly, colocalization of ID1 with centrosomes (i.e. with γ-tubulin) was more obvious in leukemic cells expressing higher levels of endogenous ID1 (Additional file 1).

Bottom Line: ID1 protein is localized at the centrosomes and forced (over-)expression of ID1 results in errors during centrosome duplication.While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4.Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany.

ABSTRACT

Background: ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-)expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID1 have been detected in multiple human malignancies, and in some have been correlated with unfavorable clinical prognosis. ID1 protein is localized at the centrosomes and forced (over-)expression of ID1 results in errors during centrosome duplication.

Results: Here we analyzed the steady state expression levels of the four ID-proteins in 18 tumor cell lines and assessed the number of centrosome abnormalities. While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4. Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed.

Conclusions: This is the first report that shows that not only ectopic expression in tissue culture but endogenous levels of ID1 modulate centrosome numbers. Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness.

Show MeSH
Related in: MedlinePlus