Protein tyrosine phosphatase PTP1B is involved in neuroendocrine differentiation of prostate cancer.
BACKGROUND
Prostate cancer (PC) contains a minor component of neuroendocrine (NE) cells that may stimulate androgen-independent growth of the tumor. The mechanism of neuroendocrine differentiation remains unknown.


METHODS
The expression of PTP1B, a protein tyrosine phosphatase, was studied in LNCaP cells induced to show neuroendocrine phenotype by androgen withdrawal. Wild-type PTP1B and its dominant-negative mutant were transfected into LNCaP cells to study their effects on neuroendocrine differentiation. In vivo expression of PTP1B in human prostate cancer was studied by immunohistochemistry.


RESULTS
Androgen withdrawal of LNCaP cells led to increased expression of PTP1B with a corresponding increase in its tyrosine phosphatase activity. Overexpression of PTP1B in LNCaP cells led to neuroendocrine differentiation while expression of its dominant-negative mutant inhibited neuroendocrine differentiation. Immunohistochemical study showed that PTP1B was exclusively expressed in neuroendocrine cells of human prostate cancer tissue.


CONCLUSIONS
Our findings suggest that PTP1B plays an important role in neuroendocrine differentiation, and therefore, may possibly be involved in the progression of prostate cancer.
Wu
Chengyu
C
Department of Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Zhang
Li
L
Bourne
Patricia A
PA
Reeder
Jay E
JE
di Sant'Agnese
P Anthony
PA
Yao
Jorge L
JL
Na
Yanqun
Y
Huang
Jiaoti
J
D000728:Androgens / Q000008:administration & dosage; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009490:Neurosecretory Systems / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D000728:Androgens; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases