Abstract
Id-1 is a member of the helix-loop-helix family of proteins that regulates the activity of transcription factors to suppress cellular differentiation and to promote cell growth. Overexpression of Id-1 in tumor cells correlates with increased malignancy and resistance to chemotherapy and radiotherapy. Id-1B is an isoform generated by alternative splicing that differs from the classical Id-1 in the 13-C-terminal amino acids, whose function is at present unknown. We have studied the role of Id-1B in cancer and its expression in healthy/malignant lung tissues. Overexpression of Id-1B in A549 lung and PC3 prostate cancer cells reduced anchorage-dependent and independent proliferation and clonogenic potential. Moreover, it increased the proportion of cells in the G0/G1 phase of the cell cycle and p27 levels, while reduced phospho-Erk and cyclin A levels. Through microarray analysis, we identified genes involved in cell growth and proliferation that are specifically deregulated as a consequence of Id-1B overexpression, including IGF2, BMP4, Id2, GATA3, EREG and AREG. Id-1B overexpressing cells that were treated with 4Gy irradiation dose were significantly less resistant to cell death. In vivo assays demonstrated that tumors with high Id-1B levels exhibited less growth (p<0.01), metabolic activity (glucose uptake) and angiogenesis (p<0.05) compared to tumors with low Id-1B expression; mice survival was significantly extended (p<0.05). Quantification by qRT-PCR revealed that expression of Id-1B was significantly lower (p<0.01) in human lung tumors compared to their matched nonmalignant counterparts. In conclusion, our results demonstrate that Id-1B decreases the malignancy of lung and prostate cancer cells, sensitizes them to radiotherapy-induced cell death, and counteracts the protumorigenic role of the classical form of Id-1.
| Original language | English |
|---|---|
| Pages (from-to) | 151-162 |
| Number of pages | 12 |
| Journal | Current Molecular Medicine |
| Volume | 14 |
| Issue number | 1 |
| State | Published - Jan 14 2014 |
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Keywords
- Angiogenesis
- Id-1
- Lung cancer
- Prostate cancer
- Radiotherapy
- Splicing
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Molecular Medicine
Cite this
Id-1B, an alternatively spliced isoform of the inhibitor of differentiation-1, impairs cancer cell malignancy through inhibition of proliferation and angiogenesis. / Nguewa, P.; Manrique, I.; Díaz, R.; Redrado, M.; Parrondo, R.; Perez-Stable, Carlos; Calvo, A.
In: Current Molecular Medicine, Vol. 14, No. 1, 14.01.2014, p. 151-162.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Id-1B, an alternatively spliced isoform of the inhibitor of differentiation-1, impairs cancer cell malignancy through inhibition of proliferation and angiogenesis
AU - Nguewa, P.
AU - Manrique, I.
AU - Díaz, R.
AU - Redrado, M.
AU - Parrondo, R.
AU - Perez-Stable, Carlos
AU - Calvo, A.
PY - 2014/1/14
Y1 - 2014/1/14
N2 - Id-1 is a member of the helix-loop-helix family of proteins that regulates the activity of transcription factors to suppress cellular differentiation and to promote cell growth. Overexpression of Id-1 in tumor cells correlates with increased malignancy and resistance to chemotherapy and radiotherapy. Id-1B is an isoform generated by alternative splicing that differs from the classical Id-1 in the 13-C-terminal amino acids, whose function is at present unknown. We have studied the role of Id-1B in cancer and its expression in healthy/malignant lung tissues. Overexpression of Id-1B in A549 lung and PC3 prostate cancer cells reduced anchorage-dependent and independent proliferation and clonogenic potential. Moreover, it increased the proportion of cells in the G0/G1 phase of the cell cycle and p27 levels, while reduced phospho-Erk and cyclin A levels. Through microarray analysis, we identified genes involved in cell growth and proliferation that are specifically deregulated as a consequence of Id-1B overexpression, including IGF2, BMP4, Id2, GATA3, EREG and AREG. Id-1B overexpressing cells that were treated with 4Gy irradiation dose were significantly less resistant to cell death. In vivo assays demonstrated that tumors with high Id-1B levels exhibited less growth (p<0.01), metabolic activity (glucose uptake) and angiogenesis (p<0.05) compared to tumors with low Id-1B expression; mice survival was significantly extended (p<0.05). Quantification by qRT-PCR revealed that expression of Id-1B was significantly lower (p<0.01) in human lung tumors compared to their matched nonmalignant counterparts. In conclusion, our results demonstrate that Id-1B decreases the malignancy of lung and prostate cancer cells, sensitizes them to radiotherapy-induced cell death, and counteracts the protumorigenic role of the classical form of Id-1.
AB - Id-1 is a member of the helix-loop-helix family of proteins that regulates the activity of transcription factors to suppress cellular differentiation and to promote cell growth. Overexpression of Id-1 in tumor cells correlates with increased malignancy and resistance to chemotherapy and radiotherapy. Id-1B is an isoform generated by alternative splicing that differs from the classical Id-1 in the 13-C-terminal amino acids, whose function is at present unknown. We have studied the role of Id-1B in cancer and its expression in healthy/malignant lung tissues. Overexpression of Id-1B in A549 lung and PC3 prostate cancer cells reduced anchorage-dependent and independent proliferation and clonogenic potential. Moreover, it increased the proportion of cells in the G0/G1 phase of the cell cycle and p27 levels, while reduced phospho-Erk and cyclin A levels. Through microarray analysis, we identified genes involved in cell growth and proliferation that are specifically deregulated as a consequence of Id-1B overexpression, including IGF2, BMP4, Id2, GATA3, EREG and AREG. Id-1B overexpressing cells that were treated with 4Gy irradiation dose were significantly less resistant to cell death. In vivo assays demonstrated that tumors with high Id-1B levels exhibited less growth (p<0.01), metabolic activity (glucose uptake) and angiogenesis (p<0.05) compared to tumors with low Id-1B expression; mice survival was significantly extended (p<0.05). Quantification by qRT-PCR revealed that expression of Id-1B was significantly lower (p<0.01) in human lung tumors compared to their matched nonmalignant counterparts. In conclusion, our results demonstrate that Id-1B decreases the malignancy of lung and prostate cancer cells, sensitizes them to radiotherapy-induced cell death, and counteracts the protumorigenic role of the classical form of Id-1.
KW - Angiogenesis
KW - Id-1
KW - Lung cancer
KW - Prostate cancer
KW - Radiotherapy
KW - Splicing
UR - http://www.scopus.com/inward/record.url?scp=84891851424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84891851424&partnerID=8YFLogxK
M3 - Article
C2 - 24295493
AN - SCOPUS:84891851424
VL - 14
SP - 151
EP - 162
JO - Current Molecular Medicine
JF - Current Molecular Medicine
SN - 1566-5240
IS - 1
ER -