Novel Pathways Associated with Bypassing Cellular Senescence in Human Prostate Epithelial Cells

Authors

• Steven R. Schwarze, University of Wisconsin Medical School
• Samuel E. DePrimo, Stanford University
• Lisa M. Grabert, Marquette UniversityFollow
• Vivian X. Fu, University of Wisconsin Medical School
• James D. Brooks, Stanford University
• David F. Jarrard, University of Wisconsin Medical School

Document Type

Article

Publication Date

4-2002

Publisher

American Society for Biochemistry and Molecular Biology

Source Publication

Journal of Biological Chemistry

Source ISSN

0021-9258

Abstract

Cellular senescence forms a barrier that inhibits the acquisition of an immortal phenotype, a critical feature in tumorigenesis. The inactivation of multiple pathways that positively regulate senescence are required for immortalization. To identify these pathways in an unbiased manner, we performed DNA microarray analyses to assess the expression of 20,000 genes in human prostate epithelial cells (HPECs) passaged to senescence. These gene expression patterns were then compared with those of HPECs immortalized with the humanPapillomavirus 16 E7 oncoprotein. Senescent cells display gene expression patterns that reflect their nonproliferative, differentiated phenotype and express secretory proteases and extracellular matrix components. A comparison of genes transcriptionally up-regulated in senescence to those in which expression is significantly down-regulated in immortalized HPECs identified three genes: the chemokine BRAK,DOC1, and a member of the insulin-like growth factor axis,IGFBP-3. Expression of these genes is found to be uniformly lost in human prostate cancer cell lines and xenografts, and previously, their inactivation was documented in tumor samples. Thus, these genes may function in novel pathways that regulate senescence and are inactivated during immortalization. These changes may be critical not only in allowing cells to bypass senescence in vitrobut in the progression of prostate cancer in vivo.

Comments

Published version. Journal of Biological Chemistry, Vol. 277, No. 17 (April 2002): 14877-14883. DOI. © 2002 The American Society for Biochemistry and Molecular Biology, Inc. Used with permission.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Schwarze, Steven R.; DePrimo, Samuel E.; Grabert, Lisa M.; Fu, Vivian X.; Brooks, James D.; and Jarrard, David F., "Novel Pathways Associated with Bypassing Cellular Senescence in Human Prostate Epithelial Cells" (2002). College of Nursing Faculty Research and Publications. 1109.
https://epublications.marquette.edu/nursing_fac/1109