Cathepsin D protein levels in colorectal tumors: Divergent expression patterns suggest complex regulation and function

  • Authors:
    • Christine Iacobuzio-Donahue
    • Sania Shuja
    • Jinguo Cai
    • Phyllis Peng
    • John Willett
    • Mary Jo Murnane
  • View Affiliations

  • Published online on: March 1, 2004     https://doi.org/10.3892/ijo.24.3.473
  • Pages: 473-485
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Cathepsin D protein patterns were analyzed in 59 colorectal tumors by Western blotting, glycosylation and immunohistochemical assays. Measurement of protein content by laser densitometry of tumor/normal pairs on Western blots revealed loss of cathepsin D protein in more than 50% of colorectal tumors. Independent loading controls and statistical estimates of reproducibility on duplicate assays confirmed frequent decreases in cathepsin D. For cases having a tumor/normal ratio (T/N) <1, the average T/N was 0.50±0.19, equivalent to the loss of one cathepsin D allele. However, 2-fold increases in cathepsin D protein levels were also observed in approximately 1/3 of tumors, supporting the concept that colorectal cancers develop via divergent molecular pathways and that cathepsin D may function differently in different cancers. Although normal cathepsin D expression was detected in some earlier stage tumors, protein levels became increasingly bimodal with progression such that cathepsin D levels were increased in 1/3 but decreased in 2/3 of stage III and IV cancers. Other laboratories have reported both significant loss and gain of chromosome 11 (site of the cathepsin D gene) in different colorectal tumors, providing a possible mechanism for our observations on cathepsin D. However, differential regulation of cathepsin D expression by mutant versus wild-type p53 may also contribute to variable cathepsin D levels in colorectal cancers. Immunohistochemical studies demonstrated a shift from a predominantly punctate distribution of cathepsin D protein in normal mucosa to a more diffuse cytoplasmic distribution in tumor tissues. Mutant forms of cathepsin D were not detected in tumors either as changes in electrophoretic mobility or altered glycosylation but minor changes in protein sequence could not be ruled out. Loss of cathepsin D protein may provide an advantage to colorectal tumors related to a loss of cathepsin D function in proapototic or antiangiogenic pathways while increased cathepsin D may promote cancer cell proliferation or invasion.

Related Articles

Journal Cover

March 2004
Volume 24 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Iacobuzio-Donahue, C., Shuja, S., Cai, J., Peng, P., Willett, J., & Murnane, M.J. (2004). Cathepsin D protein levels in colorectal tumors: Divergent expression patterns suggest complex regulation and function. International Journal of Oncology, 24, 473-485. https://doi.org/10.3892/ijo.24.3.473
MLA
Iacobuzio-Donahue, C., Shuja, S., Cai, J., Peng, P., Willett, J., Murnane, M. J."Cathepsin D protein levels in colorectal tumors: Divergent expression patterns suggest complex regulation and function". International Journal of Oncology 24.3 (2004): 473-485.
Chicago
Iacobuzio-Donahue, C., Shuja, S., Cai, J., Peng, P., Willett, J., Murnane, M. J."Cathepsin D protein levels in colorectal tumors: Divergent expression patterns suggest complex regulation and function". International Journal of Oncology 24, no. 3 (2004): 473-485. https://doi.org/10.3892/ijo.24.3.473