Download 1,25-Dihydroxyvitamin D3Receptors in Human

(CANCER RESEARCH 51. 2021-2024. April 15. 1991]
1,25-Dihydroxyvitamin D3 Receptors in Human Carcinomas: A Pilot Study1
Maria Sandgren,2 Lorraine Danforth/ Terry F. Piasse,4 and Hector F. DeLuca5
Department ofBiochemistry,
L'niversity of H'isconsin-Mauison, Madison, Wisconsin 53706
Furthermore, an epidemiological study found dietary vitamin
D and calcium intake to be inversely correlated with the risk of
1,25-Dihydroxy vitamin Dj |1,25-(OH)2D.,| receptor concentration was
colorectal cancer (12). In a study of primary carcinoma of the
measured by an accurate immunoradiometric assay in primary tumors
breast, VDR-positive tumors were found to be associated with
from 10 patients with colorectal carcinoma and 11 patients with nonlonger disease-free survival than those with receptor-negative
small cell carcinoma of the lung. Measurements were also performed on
tumors,
thus implying a prognostic value of VDR measure
a noncancerous sample of the same origin as the tumor from each patient.
All of the tumors contained receptor with a mean concentration of 123.4 ments (13).
In this study we measured VDR in surgically obtained tumors
fmol/mg protein for colorectal and 75.1 fmol/mg protein for lung carci
noma. Compared to normal tissue from the same patient, 100% of the
and adjacent normal tissue from the same patient using an
IRMA (14) and by ligand-binding assay (15). We chose to study
lung tumors and 70% of the colorectal tumors had significantly higher
levels of the 1,25-dihydroxyvitamin D.i receptor. A correlation was found tumors from colon and lung and malignant melanoma of the
between well-differentiated colorectal tumors with no or few métastases skin, since functional 1,25-(OH)2D, receptors have been iden
and high levels of 1,25-dihydroxyvitamin D.i receptor. Receptor concen
tified in tumor cell lines derived from these tissues (5), com
tration was also assayed in metastatic lesions of malignant melanoma
bined with a relatively high incidence in the population (16).
from 7 patients. 1,25-Dihydroxy vitamin Dj receptor was present in 85%
The aim of the study was to investigate whether 1,25of the métastasesat a mean level of 26 fmol/mg protein. For these
(OH):D,
receptor number is altered as a result of malignant
patients an inverse correlation was found between receptor level and age.
transformation
and whether VDR measurements could be used
The results obtained in this pilot study suggest that an alteration in
1,25-dihydroxyvitamin Dj receptor regulation may occur in rivo when a as a prognostic marker to furnish a basis for endocrine therapy.
ABSTRACT
cell undergoes malignant transformation.
MATERIALS AND METHODS
INTRODUCTION
The active form of vitamin D, 1,25-(OH)2D,,6 is believed to
act through an intracellular receptor to modulate transcription
of specific genes in a manner analogous to that of other steroid
hormones (1, 2). In recent years, the presence of a specific VDR
has been demonstrated in a number of cell lines and tissues of
both normal and malignant origin (3, 4). Both in vitro and in
vivo evidences suggest that l,25-(OH):D.i plays a role in cell
replication and differentiation (5). There is evidence that VDR
is essential for these responses to 1,25-(OH)2D, and that the
magnitude of the response appears to be correlated to receptor
number (6, 7). In vitro, the hormone has been shown to inhibit
the replication of cell lines derived from cancers of the breast
and malignant melanomas (8), as well as promoting the human
colon carcinoma cell line HT-29 to differentiate into functional
enterocytes (9). Several in vivo studies also indicate a hormone
dependency of VDR-positive tumors and tissues. Experiments
in immunosuppressed mice showed that injection of 1,25(OH):D, suppresses the growth of human colon cancer xenografts and a metabolite of vitamin D was found to prolong the
survival time of mice with Lewis lung carcinoma (10, 11).
Received 10/18/90; accepted 2/4/91.
The costs of publication of this article were defrayed in part by the payment
of page charges. This article must therefore be hereby marked attMTtìstmtntin
accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
' This work was supported in part by Program Project DK-14881 from the
NIH. by a grant from the National Foundation for Cancer Research, by a grant
from Unimed. Inc.. and by Project Grant 3032-B9I-OI PAC from the Swedish
Cancer Foundation.
2 Present address: Department of Medical Nutrition. Karolinska Institute.
Huddinge University Hospital. S-141 86 Huddinge, Sweden.
3 Present address: Clinical Oncology. University Hospitals. K4/642 Clinical
Science Center. Madison. WI 53706.
4 Present address: Unimed, Inc., 35 Columbia Road. Somervillc. NJ 088763587.
5To whom correspondence should be addressed, at Department of Biochem
istry, University of Wisconsin-Madison, 420 Henry Mall. Madison. VVI53706.
6 The abbreviations used are: 1.25-(OH)2Dj, 1,25-dihydroxyvitamin Dt; VDR.
l,25-(OH)jDj receptor: IRMA, immunoradiometric assay: PBS. phosphate-buff
ered saline: TED. 50 mM Tris-HCl, pH 7.4-1.5 mM EDTA-5 msi dithiothreitol:
TEDK300, TED + 300 mM KCI.
Vitamin D Compounds. Radioactive 1,25-(OH)2D, (160 Ci/mmol; 1
Ci = 37 GBq) was produced by DuPont/NEN and prepared as described
previously (17). Nonradioactive l,25-(OH)2Dj was a gift from Hoff
mann-La Roche (Nutley, NJ).
Buffers. Buffers used were: PBS (1.5 mM KH:PO4-8.1 mM Na2HPO4,
pH 8.0-137 mM NaCl-2.7 mM KCI; PBS-0.5% (v/v) Triton X-100; 50
mM Tris-HCl, pH 7.4-1.5 m.M EDTA; TED; TED-150 mM NaCl;
TEDK300; TEDK300-0.5% (w/v) bovine serum albumin-0.02% NaN,;
TEDK300-5 mM diisopropyl fluorophosphate.
Sample Preparation. Tissues were surgically excised, trimmed free of
muscularis, and immediately taken to the Pathology Department (Uni
versity of Wisconsin-Madison) where samples of control and tumor
tissues were obtained. Specimens were frozen in liquid nitrogen or on
dry ice and stored at -70°C until use. All steps in tumor extract
preparation were carried out at 0-4°Cunless otherwise noted. Frozen
tissue was cut into small pieces with a razor blade, washed twice with
15 ml TED-50 mM NaCl and once with 15 ml TED, followed by
homogenization in 2 volumes (v/v) TEDK300-5 mM diisopropyl fluo
rophosphate, using 6-8 strokes with a glass-Teflon homogenizer. Homogenate was centrifuged for 1 h at 170,000 x g in a Beckman L5-50
ultracentrifuge and the supernatant was frozen in liquid nitrogen and
stored at -70°C.
Clinical Staging of Tumors. Colorectal cancers were staged according
to a modified Dukes' classification of carcinomas (18). Lung cancers
were staged I-III based on a tumor-nodes-metastasis classification (19).
Immunoradiometric Assay. The immunoradiometric assay was car
ried out as described previously (14). Briefly, tumor sample was mixed
with a biotinylated monoclonal antibody (VD2F12) and a second, 125Ilabeled monoclonal antibody (IVG8C11) directed against a different
and nonadjacent epitope (20). After incubation overnight at +4°C,
avidin-Sepharose was added. The mixture was kept on ice for l h with
mixing every 20 min. The Sepharose was precipitated by centrifugation
at 800 x g for 5 min and the pellet was washed 3 times with PBS-0.5%
(v/v) Triton and then counted in a Packard Multi-Prias Auto-Gamma
counter (Packard Instruments, Downers Grove, IL). Nonspecific bind
ing (i.e., incubation mixture without receptor) was subtracted from all
sample values. Receptor concentration in the sample was determined
from a standard cune using purified receptor.
Assay of Specific |'H|-l,25-(OH)2D,-binding Capacity. Samples were
diluted in 3 volumes (v/v) TEDK300 and 0.5 ml was labeled with 1 nM
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1,25-DIHYDROXYVlTAMIN
l,25-(OH)2-[26,27-'H]D., overnight at +4°C. Parallel samples were
incubated in the presence of 100 n\i l,25-(OH)2D.i to assess nonspecific
binding. Receptor-bound hormone was separated from unbound hor
mone by a modified (21) hydroxyapatite assay (15, 22). Bound radio
activity was counted in a Packard Prias 400 CL/D liquid scintillation
counter (Packard Instruments).
Protein Assay. Protein concentration in tumor preparations was
measured by Bio-Rad Microassay using bovine serum albumin as a
standard.
Table 1 Determination of VDR levels in colorectal carcinomas and normal
colorectal mucosa by IRMA and ligand binding assay
Data are expressed as the mean of >3 determinations ±SD for IRMA and as
the mean of duplicate determinations for hydroxy lapatite assay. Values for normal
mucosa are in parentheses.
stage
binding
(Duke's)C2B2BlC2ClB2C2B2C2B2IRMA(fmol/mg)90
Patient5065"5115°5143°515651795182"5196"5197"52025255°Age(yr)7267756365675973487
(fmol/mg)35.5
RESULTS
difference (P < 0.05) between ratios of the two groups was
observed using the Mann-Whitney U test, where a higher ratio
was correlated to a more differentiated tumor with few or no
métastases.No significant correlation could be found between
age and VDR levels in either normal mucosa or tumors (data
not shown). However, the small number of samples available
for this study is a major limitation to any conclusions that can
be drawn with regard to correlations between VDR levels, age,
or tumor stage.
Lung Cancer. Primary carcinomas and normal lung paren
chyma from 11 patients were analyzed. Nine of the tumors
were adenocarcinomas and two were squamous cell carcinomas.
One of the patients was female and the age range was 47-82
years.
When analyses were done by IRMA, all tumor samples and
10 of 11 normal samples were found to contain VDR. Normal
lung had between 0 and 21 fmol VDR/mg protein with a mean
of 11.0, while the tumors contained 16 to 173 fmol/mg protein
with a mean of 75.1 (Table 2). By using the ligand-binding
assay, only 1 of 11 normal samples showed specific 1,25(OH)2D, binding activity, 9 of 11 had no binding activity (<3
fmol/mg protein), and in one case the limited amount of
±3.3
5.5)194
(45 ±
(0)*(—
±10.4
(175
12.0)146
±
)47.3
91(70
±
±5.2)32
Colorectal Cancer. Ten primary colorectal adenocarcinomas
were analyzed. Normal colorectal mucosa from the same pa
tients served as an "internal control." All patients were male
ranging in age between 48 and 77 years.
Using the IRMA we detected VDR in all normal and tumor
samples. Normal mucosa contained between 26 and 175 fmol
receptor/mg protein with a mean of 90 fmol/mg protein, while
tumor preparations had a mean of 123.4 fmol VDR/mg protein
ranging from 32 to 200 fmol (Table 1). There was a statistically
significant higher VDR content in the tumors than in the
normal colorectal mucosa (P < 0.05) using a paired t test. For
two patients there was no difference and in one case the normal
tissue had a higher VDR content than the corresponding tumor.
When the ligand binding assay was used to assess VDR levels,
3 normal samples and 1 tumor sample had unmeasurable quan
tities of receptor (<3 fmol/mg protein). Values ranged from 0
to 39 for normal and from 0 to 101 for tumor extracts. (The
means were 13 and 36 fmol/mg protein, respectively.) This
method revealed higher VDR levels in the tumors compared to
normal mucosa in 7 of 9 patients. One sample set showed no
difference and one had more receptor in normal mucosa. When
comparing the VDR levels of the normal group to those of the
tumor group using the Wilcoxon signed-ranks test, a difference
was indicated both by the IRMA and by the ligand binding
assay (P < 0.05).
To assess the change in receptor number between normal and
tumor tissue, we calculated the ratio of VDR in tumor sample
over VDR in control sample for each patient. The mean ratio
was 1.87 for tumors classified as Dukes' stage B and 1.18 for
tumors classified as Dukes' stage C (not shown). A significant
D RECEPTOR
(6.4)0(0)69.4
±2.5
5.0)120
(40 ±
±5.7
(173±
14.1)56
(23.6)10.2
±2.1
0.6)106
(26 ±
(0)17.9
1.4(77
±
3.8)200
±
(10.0)17.5
±12.0
(104
5.7)108
±
(13.5)28.4
±7.8
(106
2.1)182
±
(39.3)101.8
±0.7
(87 ±6.4)Ligand
(24.0)
°Statistically significant higher VDR levels in the tumor compared to control
tissue using the paired t test (P < 0.05).
* Insufficient material available for assay.
Table 2 Determination of VDR levels in lung carcinomas and normal lung
parenchyma by IRMA and ligand binding assay
Values are expressed as the mean of 53 determinations ±SD for IRMA and
as the mean of duplicate determinations for hydroxylapatite assay. Data for
normal tissue are in parentheses.
binding
Patient5131"5160°5161"5175"5198"5210°5250°5271°5277°5294°5297°Age(yr)606382
stage1IIIIIIIII11IIIIIIIRMA(fmol/mg)111
(fmol/mg)20.0
±10.5
1.2)166
(16 ±
(2.0)65.6
3.7(1
±
±0.1)173
(11.2)b(—
±1.0
(0)63
)b(-)3.9
±2.6
(18
±6.2)35
±1.7
(21
±6.4)31
(0)13.3
±1.5
0.6)16
(3 ±
(0.5)4.3
±1.2
(12±0.1)95
(0)46.2
4.0(12
±
1.4)40
±
(0.9)5.7
±4.6
(10
1.8)33
±
(1.2)17.4
±4.4
(19
4.2)63
+
(0)11.8
0.7(9±
±
1.4)Ligand
(1.1)
°Significantly higher VDR levels in the tumor compared to control tissue (P
< 0.05 using the paired ; test).
71Insufficient material available for assay.
2022
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1.25-DIHYDROXYVITAMIN
material did not allow quantitation of VDR by the ligandbinding assay. The mean VDR value in this group was 1.7 fmol
receptor/mg. In the tumor group, 9 of 11 samples contained
VDR between 3.9 and 65.6 fmol/mg protein with a mean of
10.9 fmol/mg protein. Two samples were not analyzed with
this method due to insufficient material.
By comparing the VDR levels of the tumor group with those
of the normal group using the Wilcoxon signed-ranks test, there
was a significantly higher level of VDR in the tumors as
measured both by the IRMA and by the ligand-binding assay
(P < 0.05). For all samples analyzed, the tumor contained
significantly more VDR than its corresponding control sample
(P < 0.05 with paired t test) as measured by the IRMA.
By calculating the ratio between receptor number in tumor
sample over receptor number in control sample for each patient,
we compared lung tumors of different stages with respect to
alteration in VDR levels. However, due to a large interindividual variation and a low number of samples, no significant
difference could be observed with the Mann-Whitney U test.
In lung tumors no correlation between VDR levels and age
could be found using linear regression analysis (data not
shown).
Malignant Melanoma. Due to difficulties in locating the pri
mary tumor, only metastatic lesions of malignant melanoma
were obtained from 7 patients between 31 and 80 years of age.
No internal controls were available for these tumors.
By IRMA, 6 of 7 tumors were found to contain measurable
VDR levels. The mean was 26 fmol VDR/mg protein and the
range was between 0 and 95 fmol/mg protein (Table 3). A
reverse correlation could be demonstrated between VDR levels
and age indicating higher VDR levels in tumors from younger
subjects (r = -0.8762; P < 0.01) (Fig. 1).
By ligand binding assay 4 of 5 métastasescontained VDR
with a mean of 8.8 fmol/mg and a range of 0-23 fmol/mg. Two
samples could not be analyzed because of the limited amount
of material. The relationship between tumor stage and VDR
levels was not investigated since the primary tumors were not
available.
DISCUSSION
It is now widely accepted that l,25-(OH)2Dj, apart from its
well-known role in calcium homeostasis, is involved in the
regulation of growth and differentiation of normal and malig
nant cells. It has been established that this effect is dependent
on the presence of a specific receptor for 1,25-(OH)2D,.
In our study we used an immunoradiometric assay to measure
1,25-(OH)2D, receptor in colorectal and lung carcinomas as
well as in malignant melanomas. Radioligand binding and
qualitative techniques for VDR determinations do not take into
consideration occupied receptor, inactive receptor, or receptor
that has been denatured by manipulation, thereby underesti
mating the actual receptor concentration. With the IRMA we
were able to detect VDR in 100% of the tumors investigated
even in the absence of ligand binding activity. It should be
noted, however, that only functional receptor binds ligand. A
majority of individual colorectal and lung cancers contained
significantly higher levels of VDR compared to corresponding
normal tissue. This difference was also observed when compar
ing VDR levels in the two tumor groups to VDR levels of the
control groups. These results suggest that the VDR receptor in
lung and colorectal tumors may be regulated differentially as
compared to control tissue. The mechanism behind this differ-
D RECEPTOR
Table 3 1,25-DihydroxyviÃ-aminD¡levels in metastatic malignant melanomas as
determined hy IRMA and /¡Hand-bindingassay
IRMA values are expressed as the mean of ^3 determinations ±SD. Ligandbinding data arc expressed as the mean of duplicate determinations.
binding
Patient5079508551345209523352695300Age
(yr)55808531557055IRMA(fmol/mg)18
(fmol/mg)a0a23.07.83.410.0
1.209
±
5.095
±
5.629
±
1.89
±
±0.423
±1.3Ligand
' Insufficient material available for assay.
CDc="o0H.CDOCDo:COo:L
\\*\\
\
\\\\\I\I
OinCM100-80-60-40-20-o-\\\\I\\
\-_
\X
I\I
O
20
I
I
7
40
60
80
Age (years)
Fig. 1. Correlation between VDR levels and age in metastatic malignant
melanoma. Receptor content was determined by IRMA. Values are expressed as
the mean of three or more determinations ±SD (bars) r = -0.8762: P < 0.01).
enee in VDR expression is not understood but could possibly
be used clinically as a marker for malignant transformation of
colon and lung tissue. In addition, we observed that high
tumorcontrol sample ratios for VDR may be associated with a
more favorable tumor stage in colorectal cancers (not shown).
This is in good agreement with previously published data re
porting a prodifferentiation and antiproliferative effect of 1,25(OH)iD., both i/i vitro and in vivo (5).
For other steroid hormone receptors such as the glucocorticoid receptor, a decrease in receptor levels has been reported
with age (23). Our observation that VDR levels in malignant
melanomas seem to decrease in specimens from older subjects
could be a similar age-related decline in VDR number. The
possibility that receptor levels may correlate to a more or less
favorable prognosis in malignant melanomas could not be in
vestigated at this time. However, data on clinical course and
overall survival of the patients will become available and can be
compared to VDR number of their tumors.
Carcinogenesis has been described as a multistep process that
involves activation of oncogenes in combination with loss or
inactivation of tumor suppressor genes (23, 24). The VDR
belongs to the "superfamily" of ligand-dependent transcriptional factors with demonstrated high homology to oncogenes
(22, 26). Based on accumulated data, it seems likely that the
effect of l,25-(OH);>D;i on differentiation and proliferation of
tumors may be related to the expression of specific oncogenes
thereby suppressing or promoting tumor growth. The close
relationship to oncogenes is exemplified by the finding that
2023
Downloaded from cancerres.aacrjournals.org on June 16, 2017. © 1991 American Association for Cancer Research.
1.25-DlHVDROXVVITAMlN
1,25-(OH)2D, decreases the expression of the c-myc oncogene
(4), presumably through a receptor-mediated mechanism. If
l,25-(OH):D.i via its receptor can inhibit tumor growth, VDR
determination could become a valuable marker for prognosis
and therapeutic regimen in lung and colorectal carcinomas.
Based on receptor determinations, endocrine treatment has
already proved useful in estrogen- and progesterone receptorpositive breast cancer (27). It should be noted, however, that
there are data suggesting that a certain level of receptor is
necessary to induce a cellular response to a specific hormone
(28).
Our results indicate that an alteration in VDR regulation
takes place when a normal cell undergoes malignant transfor
mation. In light of our observations, we believe that VDR
determinations could become an important tool in diagnosing,
predicting prognosis, and treating patients with lung and colo
rectal carcinomas and possibly other malignancies.
12.
13.
14.
15.
16.
17.
18.
19.
REFERENCES
1. Giguere. V., Vang, N., Segui. P., and Evans. R. M. Identification of a new
class of steroid hormone receptors. Nature (Lond.). 331: 91-94. 1988.
2. Link. R.. and DeLuca. H. F. The vitamin D receptor. In: The Receptors.
Vol. 2. pp. 1-35. New York: Academic Press. 1985.
3. Colston. K.. Colston. M. }., Fieldsteel. A. H.. and Feldman, D. 1,25Dihydroxyvitamin D, receptors in human epithelial cancer cell lines. Cancer
Res.. 42: 856-859. 1982.
4. Reiche!. H., Koeffler, H. P., and Norman, A. W. The role of the vitamin D
endocrine system in health and disease. N. Engl. J. Med.. 320: 980-991.
1989.
5. Manolagas. S. C. Vitamin D and its relevance to cancer. Anticancer Res., 7:
625-638. 1987.
6. Chen. T. L.. Hauschka. P. V.. Cabrales. S.. and Feldman. D. The effects of
1,25-dihydroxyvitamin D, and dcxamethasone on rat osteoblast-like primary
cell cultures: receptor occupancy and functional expression patterns for three
different bioresponses. Endocrinology, 118: 250-259. 1986.
7. Pike. J. W. Intracellular receptors mediate the biological action of 1,25dihydroxyvitamin D,. Nulr. Rev., 43: 161-168. 1985.
8. Frampton, R. J.. Omond. S. A., and Eisman. J. A. Inhibition of human
cancer cell growth by 1.25-dihydroxyvitamin D, metabolites. Cancer Res.,
«.•4443-4447.1983.
9. Brchier, A., and Thomasset. M. Human colon cell line HT-29: characteriza
tion of 1.25-dihydroxyvitamin D, receptors and induction of differentiation
by the hormone. J. Steroid Biochem.. 29: 265-270. 1988.
10. Eisman. J. A.. Barkla. D. H.. and Tulton. P. J. M. Suppression of in vivo
growth of human cancer solid tumor xenografts by 1.25-dihydroxyvitamin
D,. Cancer Res.. 47: 21-25. 1987.
D RECEPTOR
11. Maeda. V., V'amato, H., Mirai. T., Kobori, N., Fujii, T.. Kobayashi, Y.,
Saitoh. K-i.. Inoguchi. E.. Hakozaki. M., lijima. H., Kodaira. T.. Konai. V'.,
20.
21.
22.
23.
24.
25.
26.
27.
28.
Katoh, T.. Yoshikumi. C.. Kawai. Y., and Nomoto, K. Antitumor and other
effects of 24/?,25-dihydroxycholecalciferol in Lewis lung carcinoma causing
abnormal calcium metabolism in tumor-bearing mice. Oncology (Basel). 45:
202-205, 1988.
Garland, C., Barrett-Connor, E., Rossof. A. H.. Shekelle. R. B., Criqui. M.
H.. and Oglesby, P. Dietary vitamin D and calcium and risk of colorectal
cancer: a 19-year prospective study in men. Lancet. /: 307-309, 1985.
Colston. K. W.. Berger. U., and Coombes, R. C. Possible role for vitamin D
in controlling breast cancer cell proliferation. Lancet, /: 188-191, 1989.
Sandgren. M. E., and DeLuca, H. F. An immunoradiometric assay for 1,25dihydroxyvitamin Dj receptor. Anal. Biochem.. 183: 57-63. 1989.
Wecksler. W. R.. and Norman, A. W. An hydroxylapatite batch assay for the
quantitation of lo,25-dihydroxyvitamin
D,-receptor complexes. Anal.
Biochem.. 92: 314-323. 1979.
National Cancer Institute. Surveillance, Epidemiology and End Results:
Incidence and Mortality Data. 1973-1977. National Cancer Institute Mon
ograph. Vol. 57. Bethesda, MD: National Cancer Institute, 1981.
Napoli, J. L., Mellon, W. S., Fivizzani, M. A., Schnoes, H. K., and DeLuca.
H. F. Direct chemical synthesis of ln,25-dihydroxy|26,27-'H]vitamin
D3
with high specific activity: its use in receptor studies. Biochemistry. 79:25152521, 1980.
Astler, V. B., and Coller, F. A. The prognostic significance of direct extension
of carcinoma of the colon and rectum. Ann. Surg., 139: 846-852, 1954.
DeCaro, L. F., and Benfield, J. R. Respiratory tract neoplasms. In: A. R.
Moossa, M. C. Robson. and S. C. Schimpff (eds.). Comprehensive Textbook
of Oncology, pp. 723-743. Baltimore: Williams & Wilkins, 1986.
Dame. M. C., Pierce. E. A., Prahl. J. M.. Hayes. C. E., and DeLuca, H. F.
Monoclonal antibodies to the porcine intestinal receptor for 1.25-dihydroxy
vitamin D,: interaction with distinct receptor domains. Biochemistry, 25:
4523-4534,1986.
Dame, M. C., Pierce, E. A., and DeLuca, H. F. Identification of the porcine
intestinal 1.25-dihydroxyvitamin Di receptor on sodium dodecyl sulfate/
polyacry lamide gels by renaturation and immunoblotting. Proc. Nail. Acad.
Sci. USA. 82: 7825-7829. 1985.
Reitsma. P. H., Rothberg, P. G., Astrin. S. M., Trial, J., Bar-Shavit, Z.. Hall.
A., Teitelbaum, S. L.. and Kahn. A. J. Regulation of myc gene expression in
HL-60 leukaemia cells by a vitamin D metabolite. Nature (Lond.), 306:492494, 1983.
Chang. \V-C., and Roth, G. S. Changes in the mechanism of steroid action
during aging. J. Steroid Biochem., //: 889-892, 1979.
Sager. R. Tumor suppressor genes: the puzzle and the promise. Science
(Washington DC), 240: 1406-1412. 1989.
Weinberg, R. A. Oncogenes, antioncogenes, and the molecular bases of
multistep carcinogenesis. Cancer Res., 49: 3713-3721. 1989.
Green, S., Walter. P.. Kumar. V.. Krust. A., Bornert. J-M.. Argos. P., and
Chambón, P. Human oestrogen receptor cDNA: sequence, expression and
homology to v-fre-A. Nature (Lond.). 320: 134-139. 1986.
Osborne, C. K., Yochmovitz, M. G., Knight. W. A., and McGuire, W. L.
The value of estrogen and progesterone receptors in the treatment of breast
cancer. Cancer. 46: 2884-2888. 1980.
Vanderbilt. J. N., Miesfeld, R.. Maler. B. A., and Vaniamolo. K. R. Intra
cellular receptor concentration limits glucocorticoid-dependent enhancer ac
tivity. Mol. Endocrinol.. /: 68-74. 1987.
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1,25-Dihydroxyvitamin D3 Receptors in Human Carcinomas: A
Pilot Study
Maria Sandgren, Lorraine Danforth, Terry F. Plasse, et al.
Cancer Res 1991;51:2021-2024.
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