Nuclear and cytoplasmic oestrogen receptors in squamous carcinoma of the cervix

Soutter, W. P.; Pegoraro, R.J.; Green-Thompson, Randolph; Naidoo, Dhevaksha; Joubert, S. M.; Philpott, R. H.

doi:10.1038/bjc.1981.165

Cited by 26 publications

(12 citation statements)

References 15 publications

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“…Although cancer of the cervix is considered not to be responsive to steroid hormones, the normal cervix is known to respond actively to sex steroids (Soutter and Leake, 1987). The presence of oestrogen receptor was reported in all the samples of normal cervical tissue examined in premenopausal woman (Soutter et al, 1981(Soutter et al, , 1983.…”

Section: Discussionmentioning

confidence: 99%

“…An alternative hypothesis for oestrogen radiosensitization proposes that the hormone, which is concentrated in the nucleus of tumour cells, might release cytotoxic free radicals in the vicinity of the genome under the influence of radiotherapy (Soutter and Leake, 1987). However, cervical cancer cells in GI/M phase of the cell cycles are also believed to be more radiosensitive than those in G(/G, phase (Yu et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…The presence of oestrogen receptor was reported in all the samples of normal cervical tissue examined in premenopausal woman (Soutter et al, 1981(Soutter et al, , 1983. Several authors have measured ER and PgR levels in cervical cancer (see Soutter and Leake, 1987 for review). However, the proportion showing their presence have been variable.…”

Section: Discussionmentioning

confidence: 99%

“…The differences between studies may be the result of differences in method for tissue collection, differences in storage conditions, differences in assay techniques and perhaps differences in patient populations. Soutter and Leake (1987) have reported better preservation of steroid receptors when tissues are stored in a hyperosmolar glycerol buffer rather than in liquid nitrogen. In their study, using these storage conditions, oestrogen receptors were found in 45.2% of 73 squamous tumours.…”

Section: Discussionmentioning

confidence: 99%

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Oestrogen increases S-phase fraction and oestrogen and progesterone receptors in human cervical cancer in vivo

Bhattacharya

Redkar²,

Mittra³

et al. 1997

Br J Cancer

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Summary Although cancer of the cervix is traditionally considered not to be responsive to steroid hormones, an in vitro study has reported that the addition of oestrogen increased cellular proliferation in a cervix cancer cell line that was inhibited by progesterone. We investigated whether the reported in vitro effects of oestrogen and progesterone on cellular proliferation can be replicated in locally advanced cervical cancer in vivo and whether these effects, if any, are related to oestrogen and progesterone receptor (ER and PgR) content of the tumour. One hundred post-menopausal patients with locally advanced cervical cancer were systematically allocated by rotation to the four treatment groups: (1) control group receiving no treatment; (2) ethinyl oestradiol 50 gg; (3) norethisterone 5 mg; (4) a combination of ethinyl oestradiol and norethisterone. Hormone treatment (five doses) was given orally every 12 h. Tissue biopsies were taken before and 12 h after the last hormone treatment. S-phase fraction (SpF) was measured by flow cytometry, and ER and PgR were measured by enzyme immunoassay. Results were analysed using two-factor analysis of variance, the factors being oestrogen -absent or present -and progesterone -absent or present. The main effects of oestrogen were increases in SpF, ER and PgR, which were statistically significant (P= 0.0056, 0.0009 and 0.01 respectively), indicating that there is much greater change in these three parameters in the presence of oestrogen (mean changes 7.808 %, 6.258 fmol mg-' and 12.716 fmol mg-' for SpF, ER and PgR respectively) than in its absence (mean change -1.986 %, -3.041 fmol mg-' and 1.736 fmol mg-' respectively). The progestogen main effect and the oestrogen -progestogen interaction were not significant. The rise in SpF, ER and PgR in the presence of oestrogen had a correlation coefficient with the initial ER values of -0.0565, -0.2863 and -0.1230 respectively, none being statistically significant, suggesting that the oestrogen actions were not strictly related to baseline ER concentrations. The combined median baseline ER and PgR values of the four groups were 1.48 fmol mg-' and 0.80 fmol mg-' respectively. Our results show that oestrogen is capable of increasing SpF in locally advanced cervical cancer in vivo and may help to revive interest in the use of oestrogen as a radiosensitizing agent in the treatment of this disease.Keywords: cervical cancer; S-phase fraction; oestrogen receptor; progesterone receptor; radiosensitisation Carcinoma of the cervix is the commonest cancer in women in the developing world where most patients present at advanced stages when treatment with radiotherapy is not very effective (Hoskins et al, 1993). At least two studies have used adjuvant oestrogen treatment in an attempt to increase sensitivity of squamous cell carcinoma of the cervix to radiation therapy (Runge, 1959;Sugimori et al, 1976). One of these studies reported a significantly better survival in stage III patients in whom oestrogen was administered before and during radi...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Oestrogen increases S-phase fraction and oestrogen and progesterone receptors in human cervical cancer in vivo

Bhattacharya

Redkar²,

Mittra³

et al. 1997

Br J Cancer

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“…1,2) The presence of steroid hormone receptors in normal cervix [3][4][5] and cervical cancer [6][7][8] has been reported, suggesting that the cellular biological characteristics of these tissues might be associated with the actions of sex steroid hormones.…”

mentioning

confidence: 99%

Relatively High Expression Ratio of Sex Hormone‐binding Globulin Exon VII Splicing Variant to Wild‐type mRNA in Human Uterine Cervical Cancers

Misao¹,

Nakanishi²,

Fujimoto³

et al. 1998

Japanese Journal of Cancer Research

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We have demonstrated the intracellular expression of sex hormone-binding globulin (SHBG) exon VII splicing variant mRNA in human uterine cervical cancer using reverse transcription-polymerase chain reaction-Southern blot and DNA sequencing analyses. Analysis of the missing base pairs proved they corresponded to the entire exon VII, which is considered to encode a portion of the steroid-binding site, suggesting that the steroid-binding affinity of the variant protein might be different from that of the wild-type SHBG. In uterine cervical cancers, the wild-type mRNA levels were lower (P< < < <0.01) and the ratio of the SHBG variant to wild-type mRNA levels was higher (P< < < <0.01) than in the normal cervix. In cervical adenocarcinomas, the wild-type mRNA levels were higher (P< < < <0.05) and the ratio of the SHBG variant to wild-type mRNA levels was lower (P< < < <0.05) than in cervical keratinizing squamous cell carcinomas. There was no difference in expression among the clinical stages of cervical cancers. These results suggest that a relative increase of intracellular variant SHBG protein in human uterine cervical cancers might be involved in the disruption of the normal estrogen dependence. Key words: Sex hormone-binding globulin -mRNA -Splicing variant -Uterine cervical cancerThere is clinical evidence of an important role for sex steroids in the reproductive events of the uterine cervix. 1, 2)The presence of steroid hormone receptors in normal cervix [3][4][5] and cervical cancer 6-8) has been reported, suggesting that the cellular biological characteristics of these tissues might be associated with the actions of sex steroid hormones.Sex hormone-binding globulin (SHBG) is a homodimeric glycoprotein, chiefly binding to estrogen and androgen in the circulation. 9) SHBG is responsible for the transport of these hormones in human blood, and alteration of its concentration is thought to modify the bioavailability of these steroids. However, abundant evidence indicates that SHBG-steroid complex also plays a direct role in intracellular steroidal actions in the target cells. [10][11][12][13][14] In addition, the expression of SHBG mRNA has been demonstrated in female reproductive organs and tumors, including uterine cervical cancer, [15][16][17][18][19] indicating its intracellular presence. The human SHBG gene is organized into eight exons separated by seven introns. 20) Screening of a human testis cDNA library revealed the presence of other clones markedly different from the full-length SHBG cDNA. 20) One of them, lacking a 208-base pair region, is an exon VII splicing variant of the SHBG gene. This clone encodes for a truncated form of SHBG, which lacks a part of the steroidbinding domain. 21) This variant is coexpressed in human uterine endometrium, 22) but its biological implication remains to be clarified.The aim of the present study was to investigate the presence of SHBG splicing variant and its biological implication in human uterine cervical cancers. MATERIALS AND METHODS MaterialsSpecimens of normal an...

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Steroid hormone receptors in carcinoma of the cervix

Hunter¹,

Longcope²,

Keough³

1987

Cancer

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To correlate the presence of specific steroid receptors with certain characteristics of cervical carcinoma, cytosol estrogen receptors (ERc) were measured in 70 cases of cervical carcinoma, and progesterone receptors (PRc) were measured in 56 of these cases; ERc and PRc were also measured in 17 normal cervices. Measurements were made using a dextran-coated charcoal technique involving a seven-point Scatchard plot analysis. In carcinoma of the cervix significant numbers of ERc (>3 fmol/mg protein) were found in 41% of the cases, and of PRc (>3 fmol/mg protein) in 30%; only 28% of the 56 cases contained both ERc and PRc. In the normal cervices, 59% contained significant levels of ERc and 41% significant levels of PRc. No correlation was found between ERc and PRc and menopausal status of the patient, stage, cell type, or histologic grade of the tumor. A weak (P = 0.063) correlation between the presence of PRc and length of survival was also found, but there was no correlation between ERc and survival. Unlike the situation for breast cancer, measurement of ERc and PRc appears to add little of value to the clinical management of cervical carcinoma.

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Nuclear and cytoplasmic oestrogen receptors in squamous carcinoma of the cervix

Cited by 26 publications

References 15 publications

Oestrogen increases S-phase fraction and oestrogen and progesterone receptors in human cervical cancer in vivo

Oestrogen increases S-phase fraction and oestrogen and progesterone receptors in human cervical cancer in vivo

Relatively High Expression Ratio of Sex Hormone‐binding Globulin Exon VII Splicing Variant to Wild‐type mRNA in Human Uterine Cervical Cancers

Steroid hormone receptors in carcinoma of the cervix

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