Association of INT2/HST1 coamplification in primary breast cancer with hormone-dependent phenotype and poor prognosis

Borg, Åke; Sigurðsson, Helgi; Clark, Gm M.; Fernö, Mårten; Fuqua, Suzanne W.; Olsson, Håkan; Killander, D.; McGurie, Wl L.

doi:10.1038/bjc.1991.28

Cited by 116 publications

(82 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of 345 primary breast carcinomas, 50% showed moderate/strong immunohistochemical staining for cyclin D1 expression which was signi®cantly associated with oestrogen receptor positivity and an improved overall survival during observation for up to 20 years (Gillett et al, 1996). Our ®ndings are in agreement with these results, and should be compared to previous investigations demonstrating a negative in¯uence of cyclin D1 gene ampli®cation on disease outcome (Borg et al, 1991;Schuuring et al, 1992b;Henry et al, 1993) and that substantial clinical and experimental evidence points to cyclin D1 as an oncogene, both by in vitro transfection experiments (Jiang et al, 1993;Hinds et al, 1994;Lovec et al, 1994b;Zhou et al, 1995), in studies of transgenetic mice overexpressing cyclin D1 (Lovec et al, 1994a;Wang et al, 1994b) and in the ®ndings of a clonal rearrangement of the gene in mantel cell lymphomas (Withers et al, 1991) and parathyreoidea adenomas (Motokura et al, 1991). The prognostic discrepancy between cyclin D1 protein expression and gene ampli®cation analysis could be due to di erences in disease stages of patients in the various studies and the problem of de®ning a truly pathological cyclin D1 overexpression and not induced by mitogenes and steroids in receptor positive tumours .…”

Section: Discussionsupporting

confidence: 89%

Deregulation of cyclin E and D1 in breast cancer is associated with inactivation of the retinoblastoma protein

et al. 1997

View full text Add to dashboard Cite

Inactivation of the retinoblastoma protein (pRB) by mutations or abnormal phosphorylation is a mechanism by which tumour cells can subdue normal growth control. Among molecules involved in control of pRB phosphorylation, cyclin D1 and E have been found to be deregulated and overexpressed in various types of cancers. In order to study the cell cycle regulatory mechanisms in breast cancer, we have analysed the protein expression of cyclin D1 and E in 114 tumour specimens from patients with primary breast cancer using Western blotting. Twenty-®ve out of 34 tumours with overexpression of cyclin E showed uniform low cyclin D1 expression, and by immunohistochemical analysis of pRB we present evidence for the existence of pRB defects in approximately 40% of these tumours in contrast to no pRB defects in the other group of tumours. This result was supported by a high protein expression of the cyclindependent kinase inhibitor p16 in 44% of the tumours with high cyclin E and low D1 expression, and all immunohistochemical pRB defect tumours showed a high p16 protein level. Additionally, an abnormal low pRB phosphorylation in relation to a high proliferative activity and loss of heterozygosity of the retinoblastoma susceptibility gene locus were found in all but one tumour with immunohistochemical defect pRB. Interestingly, tumours with high cyclin E and low D1 expression were generally oestrogen receptor negative suggesting a role for cell cycle regulators in the mechanisms leading to oestrogen independent tumour growth. Furthermore, the prognosis di ered markedly for the patients in the various groups of tumours, indicating that the heterogeneous nature of breast cancer pathogenesis and the clinical course in part could be explained by di erent and distinctive sets of cell cycle defects.

show abstract

Section: Discussionsupporting

confidence: 89%

Deregulation of cyclin E and D1 in breast cancer is associated with inactivation of the retinoblastoma protein

et al. 1997

View full text Add to dashboard Cite

show abstract

“…These carcinoma have stressed that amplification and overexpression of Dl play an important cyclin Dl correlates with poor prognosis (Borg et al, 1991;Schuuring et al, 1992b;Muller et al, 1994). The present study y demonstrated overexshows that, in patients with invasive tumours, there was a lf of 75 urinary bladder tendency for patients with overexpression of cyclin Dl to have a lification of the 1 lq13 worse prognosis than patients with negatively stained tumours for icers (Schuuring, 1995; cyclin Dl, although the correlation between the overexpression of cyclin Dl and actuarial survival was not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancers

Shin

Kong²,

Kim³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary Cyclin Dl is a cell cycle regulator essential for G1 phase progression and is frequently overexpressed in several human tumour types as a consequence of gene amplification or chromosomal rearrangements. We analysed the expression of cyclin Dl in 75 patients with transitional cell carcinoma (TCC) to investigate the possible relationship between its expression and clinical outcome as well as histopathological findings using the immunohistochemical method. We observed strong staining (++, > 50% positive cells) for cyclin Dl in 19 cases (25.3%) and weak staining (+, 5-50% positive cells) in 19 cases (25.3%). Overexpression of cyclin Dl was not associated with tumour invasion. No significant association was found between overexpression of cyclin Dl and tumour grade (P > 0.05). We assessed the differences of disease-free interval in superficial tumours and actuarial survival probability in invasive tumours according to the status of cyclin Dl expression. Tumours with (++) staining for cyclin Dl recurred much more rapidly than (-) and/or (+) staining tumours (P < 0.01 for -vs ++; P < 0.05 for + vs ++). However, overexpression of cyclin Dl was not associated with a shortened overall survival of patients with invasive tumours (P< 0.1). These results suggest that genetic alteration of cyclin Dl appears to be an early event in the tumorigenesis of bladder TCC and is associated with early recurrence in superficial tumours.

show abstract

“…ErbB2 is overexpressed in a proportion of human tumours arising from several di erent sites (Berchuck et al, 1990;Hall et al, 1990;Kern et al, 1990;Yokota et al, 1986;Yonemura et al, 1991). In the breast, the 20 ± 25% of cancers which overexpress the gene have a poorer prognosis (Borg et al, 1990;Gasparini et al, 1992;Press et al, 1993;Slamon et al, 1987;Wright et al, 1989) and are relatively resistant to hormonal treatment (Wright et al, 1992) and chemotherapy (Gusterson et al, 1992;Muss et al, 1994). In vitro, ERBB2 is a transforming oncogene, both in rodent ®broblasts (Di Fiore et al, 1987) and immortalised breast epithelial cell lines (D'Souza et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…Approximately 60% of breast cancers express oestrogen receptor (ER), and these tumours are less likely to overexpress ERBB2 (Adnane et al, 1989;Borg et al, 1990;Tandon et al, 1989). Tamoxifen is the leading hormonal treatment for breast cancer, producing objective disease responses in women with metastatic breast cancer (Hayward et al, 1977) and, in the adjuvant setting, increasing overall survival in post-menopausal women (Early Breast Cancer Trialists Collaborative Group, 1992a,b).…”

Section: Introductionmentioning

confidence: 99%

An intron 1 enhancer element mediates oestrogen-induced suppression of ERBB2 expression

Bates

Hurst

1997

Oncogene

View full text Add to dashboard Cite

Overexpression of the ERBB2 gene in human breast cancer is associated with a poor prognosis and resistance to hormonal treatment and chemotherapy. Oestrogen receptor (ER) positive tumour-derived cell lines are known to express relatively low levels of ERBB2 protein under oestrogenic conditions, but markedly higher levels following withdrawal of oestrogens or administration of tamoxifen. Expression of the closely related ERBB3 gene, which co-operates with ERBB2 in cellular transformation, is now shown to respond to oestrogenic manipulation in a similar way, both responses being mediated largely by transcriptional changes. Six previously undescribed DNase I hypersensitive sites occur within the ®rst intron of ERBB2 in cells that overexpress the gene. A 409 base pair DNA fragment containing one of these sites conferred ER dependent oestrogen inhibition on the ERBB2 promoter in two types of transient transfection assay. DNase I footprinting revealed four separate transcription factor binding sites within this fragment consistent with a role as a transcriptional enhancer. These ®ndings implicate intron 1 sequences in the control of ERBB2 expression for the ®rst time and demonstrate that one site within this region is involved in mediating the transcriptional response to oestrogens. Additionally, there is likely to be synergism between ERBB2 and ERBB3 signalling when both are overexpressed in response to oestrogen inhibition, thereby driving transformed cell behaviour.

show abstract

Association of INT2/HST1 coamplification in primary breast cancer with hormone-dependent phenotype and poor prognosis

Cited by 116 publications

References 35 publications

Deregulation of cyclin E and D1 in breast cancer is associated with inactivation of the retinoblastoma protein

Deregulation of cyclin E and D1 in breast cancer is associated with inactivation of the retinoblastoma protein

Overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancers

An intron 1 enhancer element mediates oestrogen-induced suppression of ERBB2 expression

Contact Info

Product

Resources

About