Expression and function of ATIP/MTUS1 in human prostate cancer cell lines

Prostate. 2010 Oct 1;70(14):1563-74. doi: 10.1002/pros.21192.


Background: We have previously demonstrated Ang II type 2 (AT(2)-) receptor-mediated inhibition of EGF-induced prostate cancer cell growth in androgen-dependent (LNCaP) and independent (PC3) prostate cancer cell lines.

Methods: To explore the signaling pathways involved in this inhibitory effect, we examined the interaction of the AT(2)-receptor with its novel regulatory partner ATIP using real time PCR, over-expression, siRNA and [(3)H]thymidine incorporation assays.

Results: The results in human prostate cancer cell lines demonstrate the presence of ATIP in both cell lines examined, and suggest that (i) the AT(2)-receptor through an interaction with ATIP mediates an anti-growth factor effect in both androgen-dependent and androgen-independent cell lines; (ii) ATIP expression decreases as the rate of cell growth and androgen-independence increase; and (iii) EGF may act on cell growth in part by reducing the content of ATIP present in the cells.

Conclusions: The results support our earlier proposal in normal cell lines that ATIP is an important component of the cellular response to AT(2)-receptor activation. The results further suggest that a critical level of ATIP is required to mediate the effect of AT(2)-receptor activation to inhibit EGF mediated increases in cell growth. They also suggest that EGF may in part induce cell growth by suppressing the level of ATIP expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA Primers
  • Epidermal Growth Factor / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Polymerase Chain Reaction
  • Prostatic Neoplasms / chemically induced
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Thymidine / metabolism
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism


  • DNA Primers
  • MTUS1 protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • Epidermal Growth Factor
  • Thymidine