Telomerase Activity in Human Breast Tumors

Hiyama, Eiso; Gollahon, Lauren; Kataoka, Tsuyoshi; Kuroi, Katsumasa; Yokoyama, Takashi; Gazdar, Adi F.; Hiyama, Keiko; Piatyszek, Mieczyslaw A.; Shay, Jerry W.

doi:10.1093/jnci/88.2.116

Cited by 379 publications

(227 citation statements)

References 32 publications

Supporting

Mentioning

196

Contrasting

Unclassified

Order By: Relevance

“…The application of the in vitro TRAP assay has been instrumental in furthering our knowledge of telomerase activity in cancer (Hiyama et al, 1996;1995b). Our present study suggests the in situ analysis of the essential telomerase RNA component detects tumourspeci®c patterns of expression not evident from TRAP assay studies to date.…”

Section: Discussionmentioning

confidence: 57%

Tumour specific regulation of telomerase RNA gene expression visualized by in situ hybridization

Going

Kaye

et al. 1998

Oncogene

View full text Add to dashboard Cite

Maintenance of telomere structure by the ribonucleoprotein enzyme telomerase is considered central to the development of most human cancers. However, regulatory mechanisms governing telomerase expression during oncogenesis are largely unknown. We address potential tumour-speci®c regulation of telomerase RNA gene expression by RNA in situ hybridization to over 300 tumour samples of germ cell and epithelial origin. Twenty-six per cent of non-small cell lung cancers (NSCLC), expressed detectable levels of the telomerase RNA gene (hTR), and interestingly expression was almost con®ned to squamous carcinomas (41%), being rare in pulmonary adenocarcinomas and large-cell anaplastic carcinomas (P=0.006). Low frequency hTR expression was also associated with adenocarcinoma of the breast (13%), and ovary (17%). In comparison, hTR expression was detected in 43% of cervical cancers with no signi®cant di erences in frequency between squamous-cell carcinoma and adenocarcinoma or in transitions between intraepithelial neoplasia and invasive carcinoma. In contrast to the common epithelial cancers, the malignant cells in 73% of testicular germ-cell tumours (seminomas and teratomas), expressed hTR consistent with hTR expression in normal testicular germ cells. Di erentiated tissues within ovarian germ cell tumours and in testicular teratomas lacked detectable hTR expression. These studies show that di erent tumour types have distinct patterns of hTR expression, which has implications for our understanding of mechanisms regulating telomerase activity and for targeting the telomerase RNA component as an anti-cancer therapy.

show abstract

Section: Discussionmentioning

confidence: 57%

Tumour specific regulation of telomerase RNA gene expression visualized by in situ hybridization

Going

Kaye

et al. 1998

Oncogene

View full text Add to dashboard Cite

show abstract

“…Thus, telomerase activation may indeed be occurring in DCIS, since invasive breast cancer is usually telomerase positive even in early stages (Carey et al, 1998), and limited data on atypical hyperplasia (Poremba et al, 1998) suggest that earlier lesions are telomerase negative. While the source of low but detectable levels of telomerase in ®broadenomas (Hiyama et al, 1996;Poremba et al, 1998) will need to be investigated further, these lesions do not generally pose diagnostic di culties.…”

Section: Discussionmentioning

confidence: 99%

“…Telomerase activity has been proposed as a potentially useful tumor marker in breast cancer, since it has been detected in most invasive breast cancers, but not in benign breast lesions, with the possible exception of some ®broadenomas (Kim et al, 1994;Meeker and Co ey, 1997;Nelson, 1996;Shay and Bacchetti, 1997). In several studies of primary invasive breast cancers, approximately 75 ± 95% of tumors demonstrate telomerase activity, while 5 ± 25% are telomerase-negative (Bednarek et al, 1997;Carey et al, 1998;Hiyama et al, 1996;Landberg et al, 1997;Nawaz et al, 1997). Initial results suggested that smaller, lymph nodenegative tumors were more likely to be telomerasenegative than their larger, lymph node-positive counterparts (Hiyama et al, 1996;Kim et al, 1994), and it was postulated that telomerase activity is acquired during tumor progression to metastasis (Hiyama et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…In several studies of primary invasive breast cancers, approximately 75 ± 95% of tumors demonstrate telomerase activity, while 5 ± 25% are telomerase-negative (Bednarek et al, 1997;Carey et al, 1998;Hiyama et al, 1996;Landberg et al, 1997;Nawaz et al, 1997). Initial results suggested that smaller, lymph nodenegative tumors were more likely to be telomerasenegative than their larger, lymph node-positive counterparts (Hiyama et al, 1996;Kim et al, 1994), and it was postulated that telomerase activity is acquired during tumor progression to metastasis (Hiyama et al, 1996). More recently, some studies have found correlations between telomerase activity and stage, traditional prognostic indicators, and clinical outcome in invasive breast cancer (Clark et al, 1997;Hoos et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Telomerase activity in ductal carcinoma in situ and invasive breast cancer

et al. 1999

View full text Add to dashboard Cite

The increasing number of breast carcinoma in situ detected by screening procedures makes it imperative to develop improved markers to stratify the risk of invasive cancer. Telomerase is detectable in invasive cancer, but not in normal tissues. We have microdissected frozen tissue blocks containing both DCIS and invasive cancer to assay the telomerase activity of these two lesions. The 46 available cases of concurrent DCIS and invasive breast cancer resulted in 43 DCIS samples and 38 invasive cancer samples adequate for analysis. Seventy per cent of the DCIS and all invasive cancer samples tested had detectable telomerase activity. In addition, we analysed telomerase activity in ten cases of DCIS that were not associated with invasive cancer, and detected telomerase activity in seven (70%). Mixing experiments showed no evidence of telomerase inhibitors in telomerase negative samples. Furthermore, periductal in¯ammatory in®ltrates were shown to be a potential confounding source of telomerase activity. Since DCIS lesions appear to be heterogeneous with respect to telomerase activity, and telomerase activation appears to precede the development of invasive cancer, telomerase activity may be a useful adjunct in stratifying the risk of developing invasive breast cancer in patients with DCIS.

show abstract

“…Following the development by Kim et al (1994) of an extremely sensitive PCR-based assay, telomerase activity has been found in a large variety of solid tumours, including neuroblastomas (Hiyama et al, 1995a), lung carcinomas (Hiyama et al, 1995b), hepatomas (Tahara et al, 1995a), gastric and colon carcinomas (Chadeneau et al, 1995;Hiyama et al, 1995c;Tahara et al, 1995bLi et al, 1996, breast carcinomas (Hiyama et al, 1996;Sugino et al, 1996) and brain tumours (Langford et al, 1995). In the present study, the activity of this enzyme was demonstrated in more than 90% of colorectal carcinomas in line with previous studies (Chadeneau et al, 1995;Tahara et al, 1995b;Li et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Detection of telomerase activity in exfoliated cancer cells in colonic luminal washings and its related clinical implications

Yoshida

Sugino²,

Goodison³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary Telomerase is a ribonucleoprotein capable of replacing telomeric DNA sequences that are lost at each cell division. Under normal circumstances, it is active in rapidly dividing embryonic cells and in stem cell populations but not in terminally differentiated somatic cells. Much attention has recently focused on the hypothesis that activity of this enzyme is necessary for cells to become immortal. This predicts that telomerase activity should be detectable in malignant cells and tissues but not in their normal counterparts, which slowly senesce and die. In accordance with this notion, telomerase activity has been reported in a wide range of malignancies, including those of the gastrointestinal tract, breast and lung. In the present study, we used a polymerase chain reaction (PCR)-based assay for telomerase activity, designated the 'telomeric repeat amplification protocol (TRAP)', to examine initially 35 colonic carcinomas, their corresponding normal tissues and 12 inflammatory bowel disease (IBD) lesions. We detected strong enzyme activity in 32 (92%) of the 35 colon carcinomas while there was no activity in 30 (86%) of 35 matched normal colonic tissue specimens and only very weak activity in the remainder. Four of seven specimens of ulcerative colitis and two of five Crohn's disease lesions were negative, and the rest were only weakly positive. These results led us to examine whether telomerase could be detected in carcinoma cells exfoliated into the colonic lumen. We assayed lysates of exfoliated cells in luminal washings from colectomy specimens of 15 patients with colon carcinoma and nine with IBD. Telomerase activity was detected in washings from 9 (60%) of the 15 colon carcinoma cases but not in any from cases with IBD, suggesting that it can be a good marker for the detection of colon carcinoma, possibly even in non-invasively obtained samples.

show abstract

Telomerase Activity in Human Breast Tumors

Cited by 379 publications

References 32 publications

Tumour specific regulation of telomerase RNA gene expression visualized by in situ hybridization

Tumour specific regulation of telomerase RNA gene expression visualized by in situ hybridization

Telomerase activity in ductal carcinoma in situ and invasive breast cancer

Detection of telomerase activity in exfoliated cancer cells in colonic luminal washings and its related clinical implications

Contact Info

Product

Resources

About