Human Endometrial Cancer Cell Lines Research Articles

Roles of antiestrogen binding sites in human endometrial cancer cells

Estrogen-noncompatible antiestrogen binding sites (AEBS) as well as estrogen receptors (ER), and the growth-inhibitory effect of tamoxifen were investigated in two human endometrial cancer cell lines, IK-90 and HEC-IA cells. IK-90 cells contained specific AEBS, but no ER was found in these cells. Scatchard plot analysis of AEBS in 12,000 g supernatant from IK-90 cells showed a high affinity binding site for tamoxifen ( K d :5.6 ± 1.0nM) with the maximum binding site of 457 ± 47 fmol/mg protein. However, no measurable ER or AEBS was found in HEC-IA cells. The effect of tamoxifen on the growth of cells was found to be identical in both cell lines; the addition of 10 μ M tamoxifen to culture medium was cytocidal whereas tamoxifen at lower concentrations (1 nM-1μM) did not significantly affect the growth of both IK-90 and HEC-IA cells. These results demonstrate for the first time the presence of AEBS in human endometrial cancer cells. The present results also suggest that AEBS does not play a fundamental role in mediating the growth:inhibitory effect of tamoxifen in endometrial cancer cells.

RU486, A progestin antagonist, binds to progesterone receptors in a human endometrial cancer cell line and prevents the growth inhibition by progestins

RU486, A progestin antagonist, binds to progesterone receptors in a human endometrial cancer cell line and prevents the growth inhibition by progestins

Estrone conversion rates by human endometrial cancer cell lines

Studies on estrone metabolism by long term human endometrial cancer HEC-1A and Ishikawa cell lines are reported. These cell lines grow well in epithelial mono or plurilayer form, as previously reported. Ishikawa cells appear to be estrogen responsive whereas HEC-1A appear non responsive. In our experience Ishikawa cells show high affinity—low capacity estrogen binding sites in both soluble and nuclear fractions of the same range of ZR 75-1 and of MCF7, but HEC-1A cytosols gave K d , values in the order of 10 −8-10 −9. These values are probably more representative of estrogen receptors of low affinity-high capacity (site II) and this is in agreement with previous results regarding their poor response to estrogens. These two different endometrial cancer cell lines exhibit at the same time, common and quite dissimilar metabolic patterns of estrogens. In fact, metabolic conversion studies carried out after 24th incubation at not far from physiological concentrations by using high pressure liquid chromatography in reverse phase mode plus “on line” radioactive detection showed: (a) Both these well established cell lines are fast growing in culture with sufficient morphological or biochemical stability, at least during a limited number of passages and appear a useful material for studies on steroid metabolism, (b) In both, estradiol (E 2) and estrone (E 1) were most part of converted products (more than 95%); negligible amounts of other radio-metabolites were observed, (c) Quite different conversion rates of E 1 to E 2 have been shown by HEC-1 A cells (6 times or more), with respect to Ishikawa.

Effects of estradiol on deoxyribonucleic acid polymerase alpha activity in the Ishikawa human endometrial adenocarcinoma cell line.

The effects of estradiol on DNA polymerase alpha activity were investigated in an estrogen-responsive human endometrial cancer cell line (Ishikawa) derived from a well differentiated endometrial adenocarcinoma. These cells are known to respond to estradiol by increasing progesterone receptor levels, alkaline phosphatase activity, and cell density. Four- to 5-fold increases in DNA polymerase alpha activity occurred when estradiol was added to cultures of Ishikawa cells in medium containing charcoal-treated fetal bovine serum. Maximal stimulation was achieved at 18 h during incubations with 10(-8) M estradiol, but significant effects also were found with 10(-9) and 10(-6) M. These effects were almost completely counteracted by a 100-fold excess of 4-hydroxytamoxifen. At 10(-6) M, the antiestrogen had no influence on the basal levels of DNA polymerase alpha. Medroxyprogesterone acetate (10(-6) M) was ineffective as either an enhancer of enzymatic activity or an antiestrogen when tested in combination with 10(-8) M estradiol, even in the presence of appreciable levels of specific progesterone binders. The responsiveness of the Ishikawa cells to estrogen contrasts with the lack of effects of estradiol on DNA polymerase alpha activity in another human endometrial adenocarcinoma cell line (HEC-50).

EGF Receptor gene in a human endometrial cancer cell line (Ishikawa)

EGF Receptor gene in a human endometrial cancer cell line (Ishikawa)

Cross-sensitivity between interferon and uv in human cell strains: IF r, HEC-1, and CRL1200

Correlation between susceptibility to the anticellular effect of human interferon (HuIFN) and ultraviolet (uv) lethality was examined in a set of isogeneous human cell lines (RSa and IF r cells), a human endometrial cancer cell line (HEC-1 cells), and a Xeroderma pigmentosum-derived fibroblast cell line (CRL1200 cells). IF r cells, previously established as α HuIFN-α-resistant subline by exposing HuIFN-a- and uv-sensitive RSa cells to HuIFN-α preparations, appeared more refractory to uv than did the parent RSa cells in the cell proliferation and colony-formation studies. The extent of recovery from uv-inhibited total cellular DNA synthesis and uv-induced DNA-repair synthesis was enhanced to a greater extent in IF r cells than in RSa cells. The preexposure of RSa cells to HuIFN-α enhanced uv-induced DNA-repair replication activities. HEC-1 cells, which are reportedly totally refractory to HuIFN actions, appeared most resistant to uv, in all the tests. The uv-sensitive CRL1200 cells appeared highly susceptible to HuIFN-β, in both cell proliferation and DNA-synthesis inhibition tests. These results support and extend our previous finding ( N. Suzuki, J. Nishimaki, and T. Kuwata (1982). Mutat Res. 106, 357–376) that susceptibility to the anticellular effect of HuIFN closely relates with uv lethality.

Resistance to interferon of a human adenocarcinoma cell line, HEC-1, and its sensitivity to natural killer cell action.

A human endometrial cancer cell line, HEC-1, was found to be resistant to the antiviral and anticellular action of interferon. However, HEC-1 cells were susceptible to the cytotoxicity of natural killer (NK) cells, and interferon enhanced such NK activity. When HEC-1 cells were treated with interferon, sensitivity of HEC cells to the cytotoxicity of NK cells was not suppressed.