PMID- 10619359
OWN - NLM
STAT- MEDLINE
DCOM- 20000131
LR  - 20190831
IS  - 0960-0760 (Print)
IS  - 0960-0760 (Linking)
VI  - 71
IP  - 1-2
DP  - 1999 Nov
TI  - Differential androgen sensitivity is associated with clonal heterogeneity in 
      steroid metabolism, ornithine decarboxylase regulation and IL-1alpha action in 
      mouse mammary tumor cells.
PG  - 71-81
AB  - Upon androgen deprivation, Shionogi (SC-115) mouse mammary tumors undergo 
      phenotypic changes enabling their escape from growth dependence on androgens. 
      Even within androgen-responsive cell populations, marked clonal heterogeneity is 
      observed in the trophic effects of androgens. The present study compares several 
      parameters of androgen action between three SC-115 cell clonal subpopulations 
      exhibiting high (clone 107), low (clone S1A2) and no trophic response (clone 415) 
      to androgens. These parameters pertain to (1) kinetics of androgen binding, (2) 
      metabolism of 5alpha-dihydrotestosterone (DHT), 
      5alpha-androstane-3alpha,17beta-diol (3alpha-diol) and 
      5alpha-androstane-3beta,17beta-diol (3beta-diol), (3) ornithine decarboxylase 
      (ODC) activity and (4) interleukin-1alpha (IL-1alpha) action on cell 
      proliferation. Only marginal differences in the affinity and abundance of 
      androgen-specific binding sites were detected between the three clones. While 
      clone S1A2 degraded DHT to 3alpha-diol at a much faster rate than the highly 
      androgen-sensitive 107 cells and androgen-insensitive 415 cells, differences in 
      the rates of intracrine conversion of 3alpha-diol and 3beta-diol to DHT did not 
      correlate with the ability of these steroids to stimulate cell proliferation. 
      Induction of ODC activity at the onset of exponential growth was strongly 
      DHT-dependent in 107 cells, whereas this dependence was markedly attenuated in 
      androgen-hyposensitive cells. Unexpectedly, DHT strongly repressed the marked ODC 
      induction resulting from fresh medium addition in 415 cells which show no growth 
      response to androgens. Low IL-1alpha concentrations were mitogenic in all three 
      SC-115 clones. Whereas the mitogenic action of IL-1alpha was completely 
      androgen-dependent in 107 cells, this dependence was relieved in S1A2 cells, 
      which responded to DHT and IL-1alpha in an additive fashion. Thus, clonal 
      heterogeneity in the pattern of steroid metabolism within Shionogi tumors cannot 
      solely account for loss of androgen dependence, which may rather correlate with 
      the constitutive activation of transduction pathways controlling the expression 
      of growth-associated genes (e.g. ODC) by serum growth factors, including 
      IL-1alpha.
FAU - Hida, N
AU  - Hida N
AD  - Oncology and Molecular Endocrinology Research Center, CHUL, Le Centre Hospitalier 
      Universitaire de Quebec and Laval University, Ste. Foy, Canada.
FAU - Poulin, R
AU  - Poulin R
FAU - Veilleux, R
AU  - Veilleux R
FAU - Labrie, F
AU  - Labrie F
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Androgens)
RN  - 0 (Interleukin-1)
RN  - 0 (Mitogens)
RN  - 0 (Steroids)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 3XMK78S47O (Testosterone)
RN  - 409J2J96VR (Androstenedione)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - 95PS51EMXY (Androstenediol)
RN  - EC 4.1.1.17 (Ornithine Decarboxylase)
SB  - IM
MH  - Androgens/*metabolism/pharmacology
MH  - Androstenediol/metabolism/pharmacology
MH  - Androstenedione/metabolism/pharmacology
MH  - Animals
MH  - Binding Sites
MH  - Cell Division/drug effects
MH  - Clone Cells
MH  - Dehydroepiandrosterone/pharmacology
MH  - Dihydrotestosterone/metabolism/pharmacology
MH  - Interleukin-1/pharmacology
MH  - Male
MH  - Mammary Neoplasms, Experimental/drug therapy/*metabolism
MH  - Mice
MH  - Mitogens/pharmacology
MH  - Neoplasms, Hormone-Dependent/drug therapy/*metabolism
MH  - Ornithine Decarboxylase/drug effects/*metabolism
MH  - Steroids/*metabolism
MH  - Testosterone/pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2000/01/05 00:00
MHDA- 2000/01/05 00:01
CRDT- 2000/01/05 00:00
PHST- 2000/01/05 00:00 [pubmed]
PHST- 2000/01/05 00:01 [medline]
PHST- 2000/01/05 00:00 [entrez]
AID - S0960-0760(99)00120-X [pii]
AID - 10.1016/s0960-0760(99)00120-x [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 1999 Nov;71(1-2):71-81. doi: 
      10.1016/s0960-0760(99)00120-x.