Growth of LNCaP human prostate cancer cells is stimulated by estradiol via its own receptor.
We report that growth of LNCaP human prostate cancer cells is significantly stimulated (up to 120% above control) by physiological estradiol (E2) concentrations. This growth increase appears to be comparable to that induced by either testosterone or dihydrotestosterone, as also reported by others. This paper presents novel illustrative evidence for estrogen-binding proteins and messenger RNA transcripts in LNCaP cells. In fact, 1) the reverse transcriptase-polymerase chain reaction system documented normal messenger RNA for estrogen receptors (ER); 2) the radioligand binding assay allowed the detection of high affinity, reduced capacity binding sites in both soluble and nuclear cell fractions; and 3) the immunocytochemical analysis showed a consistently intensive staining for both ER and progesterone receptors. Compared to other human estrogen-responsive mammary cancer cells, MCF7 and ZR75-1, ER expression in LNCaP cells was not significantly lower, as shown by levels of the ER transcripts, number of sites per cell, or femtomoles per mg DNA as well as the percentage and intensity of immunocytochemical staining. A relative estimate of ER expression obtained by matching LNCaP with another human prostate cancer cell line, PC3, always displayed significantly and consistently higher levels in LNCaP cells. The detection of relatively high type I ER content in either cell compartment of LNCaP cells was paralleled by a highly intensive staining for progesterone receptors. In addition, evidence that the synthetic androgen R1881 did not compete for type I binding of E2 and that any E2-induced growth was completely reversed by the pure antiestrogen ICI-182,780, but unaffected by the antiandrogen Casodex, clearly suggests that the biological response of LNCaP cells to E2 is mediated via its own receptor.
Castagnetta
L A
LA
Hormone Biochemistry Laboratory, University Medical School, Palermo, Italy.
Miceli
M D
MD
Sorci
C M
CM
Pfeffer
U
U
Farruggio
R
R
Oliveri
G
G
Calabrò
M
M
Carruba
G
G
D000726:Androgen Antagonists / Q000494:pharmacology; D001483:Base Sequence; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms; D011869:Radioligand Assay; D011959:Receptors, Estradiol / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D017931:DNA Primers; D004273:DNA, Neoplasm; D011959:Receptors, Estradiol; D013196:Dihydrotestosterone; C014290:hydroxyflutamide; D004958:Estradiol; D005485:Flutamide; D017430:Prostate-Specific Antigen