Src kinase potentiates androgen receptor transactivation function and invasion of androgen-independent prostate cancer C4-2 cells

M. Asim, I. A. Siddiqui, Bilal Hafeez, A. Baniahmad, H. Mukhtar

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Prostate cancer is one of the most prominent malignancies of elderly men in many Western countries including Europe and the United States with increasing trend worldwide. The growth of normal prostate as well as of prostate carcinoma cells depends on functional androgen receptor (AR) signaling. AR manifests the biological actions of androgens and its transcriptional activity is known to be influenced by signal transduction pathways. Here we show that Src, a nonreceptor tyrosine kinase, is overexpressed in androgen-independent prostate carcinoma C4-2 cells. Interestingly, the expression of Src was found to progressively increase (up to threefold) in transgenic adenocarcinoma of mouse prostate mice as a function of age and cancer progression. Blocking Src kinase function by a specific inhibitor, PP2, resulted in decreased AR transactivation function on two different reporters, mouse mammary tumor virus (MMTV) and prostate-specific antigen (PSA). Consistent with this, overexpression of a functional Src mutant also led to a dramatic decrease in AR transactivation potential in a hormone-dependent manner. Interference with Src function in C4-2 cells led to decreased recruitment of AR on the target gene PSA enhancer and also resulted in the abrogation of hormone-dependent PSA transcript induction. Src inhibition also led to a dramatic decrease in the cell invasion in addition to decreasing the cellular growth. We suggest that targeting Src kinase could be an effective strategy to inhibit prostate cancer growth and metastasis.

Original languageEnglish (US)
Pages (from-to)3596-3604
Number of pages9
JournalOncogene
Volume27
Issue number25
DOIs
StatePublished - Jun 5 2008

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src-Family Kinases
Androgen Receptors
Transcriptional Activation
Androgens
Prostatic Neoplasms
Prostate
Prostate-Specific Antigen
Growth
Hormones
Mouse mammary tumor virus
Carcinoma
Protein-Tyrosine Kinases
Transgenic Mice
Signal Transduction
Neoplasms
Adenocarcinoma
Neoplasm Metastasis
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Src kinase potentiates androgen receptor transactivation function and invasion of androgen-independent prostate cancer C4-2 cells. / Asim, M.; Siddiqui, I. A.; Hafeez, Bilal; Baniahmad, A.; Mukhtar, H.

In: Oncogene, Vol. 27, No. 25, 05.06.2008, p. 3596-3604.

Research output: Contribution to journalArticle

Asim, M. ; Siddiqui, I. A. ; Hafeez, Bilal ; Baniahmad, A. ; Mukhtar, H. / Src kinase potentiates androgen receptor transactivation function and invasion of androgen-independent prostate cancer C4-2 cells. In: Oncogene. 2008 ; Vol. 27, No. 25. pp. 3596-3604.
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