Characterization of a transplantable hormone-responsive human prostatic cancer xenograft TEN12 and its androgen-resistant sublines.
BACKGROUND
Models for human prostate cancer can facilitate the study of resistance to endocrine therapy, aid drug discovery, and pre-clinical assessment.


METHODS
Characteristics thought relevant to the growth in athymic nude mice of TEN12, an androgen-dependent transplantable prostatic cell line derived from a primary prostate carcinoma, and its two androgen-independent sublines, TEN12F and TEN12C, have been assessed immunocytochemically.


RESULTS
The xenografts of the parental TEN12 line are moderately differentiated with both papillary and glandular regions, pleomorphic nuclei and abundant mitotic figures and are extremely vascular. The cells express androgen receptor (AR), PSA, VEGF, EGFR, c-erbB2, and TGFalpha. Both TEN12F and TEN12C xenografts possessed a more anaplastic morphology and displayed significantly lower growth rates, reduced blood vessel density (BVD), decreased MIB-1 antigen and E-cadherin expression and increased cytoplasmic AR and HSP90 staining. Elevated EGFR (membrane) but not c-erbB2 expression was demonstrated in the TEN12F line only. Castration of mice bearing TEN12 xenografts rapidly induced the appearance of cytoplasmic AR in the cells, PSA levels decreased initially but recovered to below pre-castration levels whilst reduced TGFalpha and loss of VEGF expression was seen in the long-term castrates.


CONCLUSIONS
TEN12 and its sublines offer additional in vivo models to study the factors involved in the progression of prostatic cancer to androgen-independence.
Harper
Maureen E
ME
Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff, United Kingdom. HarperME1@Cardiff.ac.uk
Goddard
Lindy
L
Smith
Christopher
C
Nicholson
Robert I
RI
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014183:Transplantation, Heterologous
D015820:Cadherins; D066246:ErbB Receptors; D018841:HSP90 Heat-Shock Proteins; D019394:Ki-67 Antigen; D017430:Prostate-Specific Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D016211:Transforming Growth Factor alpha