Abstract
AbstractPre‐mRNA processing is an important mechanism for globally modifying cellular protein composition during tumorigenesis. To understand this process during lung cancer, expression of two key pre‐mRNA alternative splicing factors was compared in a mouse model of early lung carcinogenesis and during regenerative growth following reversible lung injury. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and alternative splicing factor/splicing factor 2 (ASF/SF2) act antagonistically to modulate splice site selection. Both hnRNP A1 and ASF/SF2 contents rose in adenomas and during injury‐induced hyperplasia compared to control lungs, as measured by immunoblotting. While both proteins increased similarly during compensatory hyperplasia, hnRNP A1 increased to a much greater extent than ASF/SF2 in tumors, resulting in a 6‐fold increase of the hnRNP A1 to ASF/SF2 ratio. Immunohistochemical analysis showed that hnRNP A1 localized exclusively within tumor nuclei, while ASF/SF2 appeared in cytoplasm and/or nuclei, depending on the growth pattern of the tumor cells. We also demonstrated cancer‐associated changes in the pre‐mRNA alternative splicing of CD44, a membrane glycoprotein involved in cell‐cell and cell‐extracellular matrix interactions. hnRNP A1 and ASF/SF2 expression is thus differentially altered in neoplastic lung cells by mechanisms that do not strictly arise from increased cell division. These changes are influenced by tumor histology and may be associated with production of variant CD44 mRNA isoforms. © 2004 Wiley‐Liss, Inc.
Bibliography
Zerbe, L. K., Pino, I., Pio, R., Cosper, P. F., DwyerâNield, L. D., Meyer, A. M., Port, J. D., Montuenga, L. M., & Malkinson, A. M. (2004). Relative amounts of antagonistic splicing factors, hnRNP A1 and ASF/SF2, change during neoplastic lung growth: Implications for preâmRNA processing. Molecular Carcinogenesis, 41(4), 187â196. Portico.
References
40
Referenced
55
{'key': 'e_1_2_7_2_2', 'volume-title': 'World Cancer Report', 'author': 'Stewart BW', 'year': '2003'}
/ World Cancer Report by Stewart BW (2003)10.1016/S0163-7258(99)00067-4
10.1038/nrm760
10.1146/annurev.biochem.72.121801.161720
10.1016/S0168-9525(00)02176-4
10.1093/nar/29.13.2850
{'key': 'e_1_2_7_8_2', 'first-page': '655', 'article-title': 'Computational analysis and experimental validation of tumor‐associated alternative RNA splicing in human cancer', 'volume': '63', 'author': 'Wang ZN', 'year': '2003', 'journal-title': 'Cancer Res'}
/ Cancer Res / Computational analysis and experimental validation of tumor‐associated alternative RNA splicing in human cancer by Wang ZN (2003){'key': 'e_1_2_7_9_2', 'first-page': '2237', 'article-title': 'Prospective detection of preclinical lung cancer: Results from two studies of heterogeneous nuclear ribonucleoprotein A2/B1 overexpression', 'volume': '3', 'author': 'Tockman MS', 'year': '1997', 'journal-title': 'Clin Cancer Res'}
/ Clin Cancer Res / Prospective detection of preclinical lung cancer: Results from two studies of heterogeneous nuclear ribonucleoprotein A2/B1 overexpression by Tockman MS (1997)10.1016/S0169-5002(03)00193-4
10.1093/carcin/bgg008
10.1002/1098-2744(200006)28:2<76::AID-MC3>3.0.CO;2-0
10.1016/S0169-5002(00)00232-4
10.1016/0092-8674(92)90477-T
10.1126/science.8085156
10.1038/sj.onc.1202671
10.1038/nm0795-635
{'key': 'e_1_2_7_18_2', 'first-page': '1108', 'article-title': 'Expression of CD44 variant exon 6 in stage I non‐small cell lung carcinoma as a prognostic factor', 'volume': '58', 'author': 'Hirata T', 'year': '1998', 'journal-title': 'Cancer Res'}
/ Cancer Res / Expression of CD44 variant exon 6 in stage I non‐small cell lung carcinoma as a prognostic factor by Hirata T (1998)10.1038/nrm1004
{'key': 'e_1_2_7_20_2', 'first-page': '2832', 'article-title': 'Butylated hydroxytoluene exposure is necessary to induce lung tumors in BALB mice treated with 3‐methylcholanthrene', 'volume': '57', 'author': 'Malkinson AM', 'year': '1997', 'journal-title': 'Cancer Res'}
/ Cancer Res / Butylated hydroxytoluene exposure is necessary to induce lung tumors in BALB mice treated with 3‐methylcholanthrene by Malkinson AM (1997)10.1016/0041-008X(79)90457-5
10.1016/S0021-9258(19)52451-6
{'key': 'e_1_2_7_23_2', 'first-page': '931', 'article-title': 'Major effect on susceptibility to urethan‐induced pulmonary adenoma by a single gene in BALB/cBy mice', 'volume': '70', 'author': 'Malkinson AM', 'year': '1983', 'journal-title': 'J Natl Cancer Inst'}
/ J Natl Cancer Inst / Major effect on susceptibility to urethan‐induced pulmonary adenoma by a single gene in BALB/cBy mice by Malkinson AM (1983)10.1016/0163-7258(89)90023-5
10.1016/0041-008X(89)90269-X
{'key': 'e_1_2_7_26_2', 'first-page': '26', 'article-title': 'Lung injury induced by butylated hydroxytoluene: Cytodynamic and biochemical studies in mice', 'volume': '36', 'author': 'Adamson IY', 'year': '1977', 'journal-title': 'Lab Invest'}
/ Lab Invest / Lung injury induced by butylated hydroxytoluene: Cytodynamic and biochemical studies in mice by Adamson IY (1977){'key': 'e_1_2_7_27_2', 'first-page': '743', 'article-title': 'Cellular derivation of lung‐tumors in sensitive and resistant strains of mice—Results at 28 and 56 weeks after urethane treatment', 'volume': '78', 'author': 'Thaete LG', 'year': '1987', 'journal-title': 'J Nat Cancer Inst'}
/ J Nat Cancer Inst / Cellular derivation of lung‐tumors in sensitive and resistant strains of mice—Results at 28 and 56 weeks after urethane treatment by Thaete LG (1987){'key': 'e_1_2_7_28_2', 'first-page': '5818', 'article-title': 'Altered expression of heterogenous nuclear ribonucleoproteins and SR factors in human colon adenocarcinomas', 'volume': '58', 'author': 'Ghigna C', 'year': '1998', 'journal-title': 'Cancer Res'}
/ Cancer Res / Altered expression of heterogenous nuclear ribonucleoproteins and SR factors in human colon adenocarcinomas by Ghigna C (1998)10.1101/gad.11.3.334
10.1101/gad.12.1.55
10.1016/0092-8674(93)90508-N
10.1080/019021401300054028
10.1006/bbrc.2000.3252
10.1006/bbrc.2000.4068
{'key': 'e_1_2_7_35_2', 'first-page': '3212', 'article-title': 'Alternative and aberrant messenger RNA splicing of the mdm2 oncogene in invasive breast cancer', 'volume': '61', 'author': 'Lukas J', 'year': '2001', 'journal-title': 'Cancer Res'}
/ Cancer Res / Alternative and aberrant messenger RNA splicing of the mdm2 oncogene in invasive breast cancer by Lukas J (2001)10.1046/j.1525-1373.1999.d01-11.x
10.1200/JCO.2001.19.2.432
{'key': 'e_1_2_7_38_2', 'first-page': '3251', 'article-title': 'Splice variants but not mutations of DNA polymerase beta are common in bladder cancer', 'volume': '62', 'author': 'Thompson TE', 'year': '2002', 'journal-title': 'Cancer Res'}
/ Cancer Res / Splice variants but not mutations of DNA polymerase beta are common in bladder cancer by Thompson TE (2002){'key': 'e_1_2_7_39_2', 'first-page': '6688', 'article-title': 'An alternatively spliced cadherin‐11 enhances human breast cancer cell invasion', 'volume': '62', 'author': 'Feltes CM', 'year': '2002', 'journal-title': 'Cancer Res'}
/ Cancer Res / An alternatively spliced cadherin‐11 enhances human breast cancer cell invasion by Feltes CM (2002)10.1002/jcp.10147
10.1074/jbc.M004692200
Dates
Type | When |
---|---|
Created | 20 years, 11 months ago (Sept. 23, 2004, 2:06 p.m.) |
Deposited | 1 year, 9 months ago (Nov. 16, 2023, 5:59 p.m.) |
Indexed | 1 year ago (Aug. 3, 2024, 1:53 a.m.) |
Issued | 20 years, 11 months ago (Sept. 23, 2004) |
Published | 20 years, 11 months ago (Sept. 23, 2004) |
Published Online | 20 years, 11 months ago (Sept. 23, 2004) |
Published Print | 20 years, 8 months ago (Dec. 1, 2004) |
@article{Zerbe_2004, title={Relative amounts of antagonistic splicing factors, hnRNP A1 and ASF/SF2, change during neoplastic lung growth: Implications for pre‐mRNA processing}, volume={41}, ISSN={1098-2744}, url={http://dx.doi.org/10.1002/mc.20053}, DOI={10.1002/mc.20053}, number={4}, journal={Molecular Carcinogenesis}, publisher={Wiley}, author={Zerbe, Laura K. and Pino, Irene and Pio, Ruben and Cosper, Pippa F. and Dwyer‐Nield, Lori D. and Meyer, Amy M. and Port, J. David and Montuenga, Luis M. and Malkinson, Alvin M.}, year={2004}, month=sep, pages={187–196} }