Publication: Expression of c-kit and kit-ligand in benign and malignant prostatic tissues
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Date
2000
Authors
Simak, R. ; Capodieci, P. ; Cohen, D.W. ; Fair, W.R. ; Scher, H. ; Melamed, J. ; Drobnjak, M. ; Heston, W.D ; Stix, U. ; Steiner, G. ; Cordon-Cardo, C.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The tyrosine kinase receptor c-kit and its
ligand [kit ligand (KL) or stem cell factor (SCF)] exert a
broad range of biological activities during organogenesis
and normal cell development. Recent studies have
revealed that altered c-kit levels occur in a variety of
malignancies and cancer cell lines. KL has also been
shown to stimulate the growth of malignant cells, as well
as to promote chemotaxis. We had previously reported
expression of KL in stroma cells of normal human
prostate.
The present study was undertaken in order to
analyze the patterns of expression of c-kit and KL in a
well characterized set of prostatic tissues, including
normal prostate (n=4), benign prostatic hyperplasia
(BPH) (n=53) and adenocarcinoma (n=46) samples. The
distribution of c-kit and KL proteins was studied by
immunohistochemical analyses, while transcript levels
were determined by in situ hybridization with specific
RNA probes on a subset of the benign and malignant
tissues referred above. In addition, reverse-transcriptase
polymerase chain reaction (RT-PCR) was performed to
determine levels of c-kit and KL expression in cultures
of epithelial and stroma cells, as well as in the prostate
cancer cell lines LNCaP, DUI45 and PC3.
c-kit protein in normal prostate was exclusively
detected in mast cells by immunohistochemistry and in
situ hybridization. However, c-kit transcripts, but not ckit
protein, were detected in low levels and with an
heterogeneous pattern in basal epithelial cells of ducts
and acini. c-kit in BPH was detected in epithelial cells in
9 of 53 (17%) specimens. c-kit protein expression in
malignant epithelial cells was identified in 1 of 46 (2%)
tumors. However, c-kit transcripts were detected in low
levels by in situ hybridization in most of the tumors
analyzed.
KL protein and transcripts in normal prostate were
detected in high levels in stroma cells. However,
epithelial cells were unreactive for anti-KL antibody, but
Offprint requests to: Dr. Carlos Cordon-Cardo, MD, PhD, Department of
Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue
New York, NY 10021, USA. Fax: 212-794-3186. e-mail: cordonc@
mskcc.org
showed low levels of KL transcripts mainly in cells of
the basal layer. Basal epithelial cells in hyperplastic
glands showed KL expression in 13 of 53 (24%)
specimens. KL protein in tumor cells was noted in 18 of
46 (39%) cases.
c-kit transcripts were not found in normal prostate
and in the 3 cancer cell lines analyzed by RT-PCR,
however, it was present in cultured epithelial cells of
BPH, and in cultures of stroma cells from both normal
and BPH. The majority of cultured cell lines of epithelial
and stromal origin displayed considerable levels of KL.
In addition all prostate cell lines studied showed
significant levels of KL transcripts.
In summary, CO-expression of c-kit and KL in a
subset of BPH cases may suggest an autocrine mode of
signaling. Data from this study reveals that altered
patterns of c-kit and KL expression are associated with
BPH and adenocarcinoma of prostate. It appears that KL
induces mast cells proliferation and maturation and
enhances their release of protease. This could explain the
accumulation of mast cells at tumor sites. a phenomenon
that was not observed in normal prostate or BPH
samples.
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