PMID- 18223692
OWN - NLM
STAT- MEDLINE
DCOM- 20080624
LR  - 20211020
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 27
IP  - 25
DP  - 2008 Jun 5
TI  - Src kinase potentiates androgen receptor transactivation function and invasion of 
      androgen-independent prostate cancer C4-2 cells.
PG  - 3596-604
LID - 10.1038/sj.onc.1211016 [doi]
AB  - 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.
FAU - Asim, M
AU  - Asim M
AD  - Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA.
FAU - Siddiqui, I A
AU  - Siddiqui IA
FAU - Hafeez, B B
AU  - Hafeez BB
FAU - Baniahmad, A
AU  - Baniahmad A
FAU - Mukhtar, H
AU  - Mukhtar H
LA  - eng
GR  - P50 DK065303/DK/NIDDK NIH HHS/United States
GR  - R01CA101039/CA/NCI NIH HHS/United States
GR  - R01 CA101039/CA/NCI NIH HHS/United States
GR  - P50DK065303-01/DK/NIDDK NIH HHS/United States
GR  - R01CA78809/CA/NCI NIH HHS/United States
GR  - R01 CA078809/CA/NCI NIH HHS/United States
GR  - R01CA120451/CA/NCI NIH HHS/United States
GR  - R01 CA120451/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080128
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Androgens)
RN  - 0 (Receptors, Androgen)
SB  - IM
MH  - Androgens/metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - *Gene Expression Regulation, Enzymologic
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Models, Biological
MH  - Neoplasm Invasiveness
MH  - Prostatic Neoplasms/metabolism/*pathology
MH  - Receptors, Androgen/*metabolism
MH  - Transcription, Genetic
MH  - Transgenes
PMC - PMC8445586
MID - NIHMS1739107
EDAT- 2008/01/29 09:00
MHDA- 2008/06/25 09:00
PMCR- 2021/09/16
CRDT- 2008/01/29 09:00
PHST- 2008/01/29 09:00 [pubmed]
PHST- 2008/06/25 09:00 [medline]
PHST- 2008/01/29 09:00 [entrez]
PHST- 2021/09/16 00:00 [pmc-release]
AID - 1211016 [pii]
AID - 10.1038/sj.onc.1211016 [doi]
PST - ppublish
SO  - Oncogene. 2008 Jun 5;27(25):3596-604. doi: 10.1038/sj.onc.1211016. Epub 2008 Jan 
      28.