scholarly journals Proliferative responses to altered 17β-hydroxysteroid dehydrogenase (17HSD) type 2 expression in human breast cancer cells are dependent on endogenous expression of 17HSD type 1 and the oestradiol receptors

2006 ◽  
Vol 13 (3) ◽  
pp. 875-884 ◽  
Author(s):  
A Jansson ◽  
C Gunnarsson ◽  
O Stål
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Hydroxysteroid Dehydrogenase ◽  
S Phase ◽  
Phase Fraction ◽  
Mcf7 Cells ◽  
Endogenous Expression

The primary source of oestrogen in premenopausal women is the ovary but, after menopause, oestrogen biosynthesis in peripheral tissue is the exclusive site of formation. An enzyme group that affects the availability of active oestrogens is the 17β-hydroxysteroid dehydrogenase (17HSD) family. In breast cancer, 17HSD type 1 and type 2 have been mostly investigated and seem to be the principal 17HSD enzymes involved thus far. The question whether 17HSD type 1 or type 2 is of greatest importance in breast tumour development is still not clear. The aim of this study was to investigate how the loss of 17HSD type 2 expression, using siRNA in the non-tumour breast epithelial cells HMEC (human mammal epithelial cells) and MCF10A, and gain of 17HSD type 2 expression, using transient transfection in the breast cancer derived cell lines MCF7 and T47D, affect oestradiol conversion and proliferation rate measured as S-phase fraction. We further investigated how this was related to the endogenous expression of 17HSD type 1 and oestradiol receptors in the examined cell lines. The oestradiol level in the medium changed significantly in the MCF7 transfected cells and the siRNA-treated HMEC cells, but not in T47D or MCF10A. The S-phase fraction decreased in the 17HSD type 2-transfected MCF7 cells and the siRNA-treated HMEC cells. The results seemed to be dependent on the endogenous expression of 17HSD type 1 and the oestradiol receptors. In conclusion, we found that high or low levels of 17HSD type 2 affected the oestradiol concentration significantly. However, the response was dependent on the endogenous expression of 17HSD type 1. Expression of 17HSD type 1 seems to be dominant to 17HSD type 2. Therefore, it may be important to investigate a ratio between 17HSD type 1 and 17HSD type 2.

scholarly journals IGF-I in human breast cancer: low differentiation stage is associated with decreased IGF-I content

2002 ◽  
pp. 813-821 ◽  
Author(s):  
E Eppler ◽  
J Zapf ◽  
N Bailer ◽  
UG Falkmer ◽  
S Falkmer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Human Breast Cancer ◽  
S Phase ◽  
Phase Fraction ◽  
Human Breast ◽  
Morphological Criteria ◽  
Igf I ◽  
Wet Weight ◽  
Differentiation Stage

OBJECTIVE: Few investigations on the potential role of IGF-I in human breast cancer have used morphological criteria, and the data presented on the localisation of IGF-I are controversial. Moreover, little information exists on a potential correlation between local IGF-I and the grade of malignancy or prognostic factors. Therefore, we investigated the immunohistochemical localisation of IGF-I in specimens of human breast cancer tumours of the ductal type, graded as G1/G2 (well-/moderately differentiated, n=115) and G3 (poorly differentiated, n=28). METHODS: IGF-I immunoreactivity was quantified using a scaling from no (-) to numerous (+++) IGF-I-immunoreactive cells. From 29 of the G1/G2 and 17 of the G3 tumours IGF-I was also measured by RIA. Cytosolic oestrogen receptor (ER) and progesterone receptor (PR) levels, and S-phase fraction were established and related to the number of IGF-I-immunoreactive cells. RESULTS: IGF-I immunoreactivity occurred predominantly in ductal epithelial cells. Of G3 tumours, 57% exhibited IGF-I immunoreactivity as compared with 84% of G1/G2 tumours. Correspondingly, the amount of IGF-I measured by RIA was significantly lower in G3 tumours (6.9+/-0.9 ng/g wet weight) than in G1/G2 tumours (10.5+/-1.1 ng/g wet weight) (P=0.031). G1/G2 tumours exhibited a higher percentage of IGF-I-immunoreactive cells (16% -, 23% +, 41% ++, 20% +++) than G3 tumours (43% -, 37% +, 12% ++, 8% +++). When comparing the - with the +++ G1/G2 tumours, the frequency of IGF-I-immunoreactive cells was related significantly to the ER (P<0.016) and the PR (P<0.008) levels. In G1/G2 and G3 tumours, the ER and PR levels increased with the amount of IGF immunoreactivity while the S-phase fraction increased with decreasing IGF-I content. In 25% of the specimens, IGF-I immunoreactivity occurred in stromal cells, but there was no obvious difference between the different types of tumours. The survival of the G1/G2 tumour patients increased with increasing numbers of IGF-I-immunoreactive cells. CONCLUSIONS: It is concluded that IGF-I is associated with the more-differentiated type of epithelial cells and that increasing dedifferentiation goes along with decreased IGF-I content. Thus, the presence of IGF-I immunoreactivity in breast cancer epithelial cells indicates a lower degree of malignancy than the lack of IGF-I.

S-phase fraction after gating on epithelial cells predicts recurrence in node-negative breast cancer

1994 ◽  
Vol 59 (1) ◽  
pp. 7-10 ◽  
Author(s):  
Sten Wingren ◽  
Olle Stå ◽  
Siw Sullivan ◽  
Ann Brisfors ◽  
Bo Nordenskjöld
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
S Phase ◽  
Phase Fraction ◽  
Node Negative ◽  
Node Negative Breast Cancer

17β-Hydroxysteroid dehydrogenase Type 1 and Type 2: Association between mRNA expression and activity in cell lines

2006 ◽  
Vol 248 (1-2) ◽  
pp. 246-249 ◽  
Author(s):  
Joanna M. Day ◽  
Helena J. Tutill ◽  
Simon P. Newman ◽  
Atul Purohit ◽  
Harshani R. Lawrence ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Lines ◽  
Hydroxysteroid Dehydrogenase ◽  
Expression And Activity

scholarly journals Characterization of 11beta-hydroxysteroid dehydrogenase activity and corticosteroid receptor expression in human osteosarcoma cell lines

1999 ◽  
Vol 161 (3) ◽  
pp. 455-464 ◽  
Author(s):  
R Bland ◽  
CA Worker ◽  
BS Noble ◽  
LJ Eyre ◽  
IJ Bujalska ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cell Lines ◽  
Primary Cultures ◽  
Hydroxysteroid Dehydrogenase ◽  
Receptor Expression ◽  
Osteosarcoma Cell ◽  
Bone Homeostasis ◽  
Rt Pcr

Studies in vitro and in vivo have shown that corticosteroids play an important role in bone physiology and pathophysiology. It is now established that corticosteroid hormone action is regulated, in part, at the pre-receptor level through the expression of isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), which are responsible for the interconversion of hormonally active cortisol to cortisone. In this report we demonstrate 11beta-HSD activity in human osteoblast (OB) cells. Osteosarcoma-derived OB cell lines TE-85, MG-63 and SaOS-2 and fibrosarcoma Hs913T cells express the type 2 isoform of 11beta-HSD, as determined by reverse transcription polymerase chain reaction (RT-PCR) and specific enzyme assays. Enzyme activity was shown to be strictly NAD dependent with a Km of approximately 71 nM; 11beta-HSD type 1 mRNA expression and enzyme activity were not detected. All four cell lines expressed mRNA for the glucocorticoid receptor (GR) and mineralocorticoid receptor, but specific binding was only detectable with radiolabelled dexamethasone (Kd=10 nM) and not aldosterone. MG-63 cells had two to three times more GR than the other OB cells, which correlated with the higher levels of 11beta-HSD 2 activity in these cells. In contrast to the osteosarcoma cell studies, RT-PCR analysis of primary cultures of human OB cells revealed the presence of mRNA for 11beta-HSD 1 as well as 11beta-HSD 2. However, enzyme activity in these cells remained predominantly oxidative, i.e. inactivation of cortisol to cortisone (147 pmol/h per mg protein at 500 nM cortisol) was greater than cortisone to cortisol (10.3 pmol/h per mg protein at 250 nM cortisone). Data from normal human OB and osteosarcoma cells demonstrate the presence of an endogenous mechanism for inactivation of glucocorticoids in OB cells. We postulate that expression of the type 1 and type 2 isoforms of 11beta-HSD in human bone plays an important role in normal bone homeostasis, and may be implicated in the pathogenesis of steroid-induced osteoporosis.

A comparison between flow cytometric assessment of S-phase fraction and Nottingham histologic grade as prognostic instruments in breast cancer

2000 ◽  
Vol 63 (1) ◽  
pp. 11-15 ◽  
Author(s):  
Marie Sundquist ◽  
Sten Thorstenson ◽  
Lars Brudin ◽  
Olle Stål ◽  
Bo Nordenskjöld
Keyword(s):  
Breast Cancer ◽  
S Phase ◽  
Histologic Grade ◽  
Phase Fraction ◽  
Flow Cytometric

scholarly journals 11?-Hydroxysteroid dehydrogenase Type 1 in obesity and Type 2 diabetes

Diabetologia ◽  
2004 ◽  
Vol 47 (1) ◽  
pp. 1-11 ◽  
Author(s):  
T. M. Stulnig ◽  
W. Waldh�usl
Keyword(s):  
Type 2 Diabetes ◽  
Hydroxysteroid Dehydrogenase

scholarly journals Lack of prognostic significance of DNA ploidy and S phase fraction in breast cancer

1992 ◽  
Vol 66 (5) ◽  
pp. 925-929 ◽  
Author(s):  
PD Stanton ◽  
TG Cooke ◽  
SJ Oakes ◽  
J Winstanley ◽  
S Holt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Ploidy ◽  
Prognostic Significance ◽  
S Phase ◽  
Phase Fraction

scholarly journals 17β-Hydroxysteroid Dehydrogenase Type 1 Is an Independent Prognostic Marker in Breast Cancer

2004 ◽  
Vol 64 (20) ◽  
pp. 7604-7609 ◽  
Author(s):  
Olayiwola O. Oduwole ◽  
Yan Li ◽  
Veli V. Isomaa ◽  
Anne Mäntyniemi ◽  
Anitta E. Pulkka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Marker ◽  
Hydroxysteroid Dehydrogenase ◽  
Independent Prognostic Marker

Expression of 3β-Hydroxysteroid Dehydrogenase Type 1 in Breast Cancer is Associated with Poor Prognosis Independent of Estrogen Receptor Status

2017 ◽  
Vol 24 (13) ◽  
pp. 4033-4041 ◽  
Author(s):  
Yuan-Ching Chang ◽  
Chi-Kuan Chen ◽  
Ming-Jen Chen ◽  
Jiunn-Chang Lin ◽  
Chi-Hsin Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Poor Prognosis ◽  
Estrogen Receptor Status ◽  
Hydroxysteroid Dehydrogenase ◽  
Receptor Status

TK1 in Cancer Progression: elucidating its influence on cellular invasion and survival

2019 ◽  
Author(s):  
Eliza E. Bitter ◽  
Michelle H. Townsend ◽  
Kary Y.F. Tsai ◽  
Carolyn I. Allen ◽  
Rachel I. Erickson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
S Phase ◽  
Wild Type ◽  
Cellular Invasion ◽  
Cancer Pathogenesis

Abstract 1. Background: The salvage pathway enzyme thymidine kinase 1 (TK1) is elevated in the serum of several different cancer types and higher expression is associated with more aggressive tumor grade. As a result, it has potential as a biomarker for diagnosis and prognosis. Recent studies indicate that TK1 may be involved in cancer pathogenesis; however, its direct involvement has not been identified. We propose to evaluate the effects of TK1 on cancer progression in vitro through measuring cellular invasion and survival of breast cancer cells.2.Methods: Breast cancer cells MDA-MB-231, HCC 1806, and MCF7 were cultured according to standard techniques. We employed the use of TK1 target siRNA and a CRISPR-Cas9 TK1 knockout plasmid to compare transfected cell lines to wild type cell lines. Protein factors in survival and invasive pathways were also tested for correlations to TK1 in BRCA RNA-seq patient data (n=1095) using the TIMER program. Cellular invasion was quantified in cell index (factor of impedance) over a 24-hour period. Cell survival was measured by apoptosis under metabolic and DNA stress using flow cytometry. All results were statistically assessed using an ANOVA or t-test in GraphPad PRISM®.3.Results: Cellular invasion assays assessing wild type and TK1 knockdown/knockout (TK1-/-) cell types showed TK1-/- cell lines had increased invasion potential (p= 0.0001). Bioinformatically, we saw a strong overall negative correlation between apoptotic factors and TK1 (p ≤ 0.05). When testing TK1 effects on cell survival we saw a protective affect under DNA stress (p ≤ 0.05), but not under metabolic stress (p= 0.0001).4.Conclusion From cell cycle analysis, we observed a shift towards S phase in TK1-/- cells. This shift to S phase would promote growth and account for the increased cellular invasion and decrease in metabolic induced stress in TK1-/- cells. We propose that cancer cells still may elicit a cancer progressive phenotype based on effects of TK1, but that a system which isolates TK1 is not effective to understand the effects. Instead, identifying protein networks inclusive of TK1 will help to elucidate its effects on cancer progression.

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