Abstract
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 inflammatory infiltrates 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.
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Abbreviations
- DCIS:
-
Ductal carcinoma in situ
- TRAP:
-
telomerase repeat amplification protocol
- TLB:
-
Telomerase lysis buffer
- ag:
-
attogram
- PCR:
-
polymerase chain reaction
- IC:
-
internal control
- RT – PCR:
-
reverse transcriptase – PCR
References
Bacchetti S and Counter CM. . 1995 Int. J. Onc. 7: 423–432.
Bednarek AK, Sahin A, AJ., B, Johnston DA and Aldaz CM. . 1997 Clin. Cancer Res. 3: 11–16
Bednenko J, Melek M, Greene EC and Shippen DE. . 1997 EMBO J. 16: 2507–2518.
Bradford MM. . 1976 Anal. Biochem. 72: 248–254.
Carey LA, Hedican CA, Henderson GS, Umbricht CB, Dome JS, Varon D and Sukumar S. . 1998 Clin. Cancer Res. 4: 435–440.
Chiu CP and Harley CB. . 1997 Proc. Soc. Exp. Biol. Med. 214: 99–106.
Clark GM, Osborne CK, Levitt D, Wu F and Kim NW. . 1997 J. Natl. Cancer Inst. 89: 1874–1881.
Flint J, Craddock CF, Villegas A, Bentley DP, Williams HJ, Galanello R, Cao A, Wood WG, Ayyub H and Higgs DR. . 1994 Am. J. Hum. Genetics 55: 505–512.
Fuji H, Zhou W and Gabrielson E. . 1996 Genes Chromosomes Cancer 16: 35–39.
Greider CW. . 1994 Curr. Opin. Genetics Dev. 4: 203–211.
Greider CW and Blackburn EH. . 1996 Sci. Am. 274: 92–97.
Hay R, Caputo J, Chen TR, Macy M, McClintock P and Reid Y. . 1994 In: ATCC Cell Lines and Hybridomas, 8 edn. American Type Culture Collection, Rockville, MD.
Hiyama E, Gollahon L, Kataoka T, Kuroi K, Yokoyama T, Gazdar AF, Hiyama K, Piatyszek MA and Shay JW. . 1996 J. Natl. Cancer Inst. 88: 116–122.
Hoos A, Hepp HH, Kaul S, Ahlert T, Bastert G and Wallwiener D. . 1998 Int. J. Cancer 79: 8–12.
Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL and Shay JW. . 1994 Science 266: 2011–2015.
Kim NW and Wu F. . 1997 Nucl. Acids Res. 25: 2595–2597.
Klingelhutz AJ. . 1997 J. Mol. Med. 75: 45–49.
Laborda J. . 1991 Nucleic Acids Res. 19: 3998.
Landberg G, Nielsen NH, Nilsson P, Emdin SO, Cajander J and Roos G. . 1997 Cancer Res. 57: 549–554.
Meeker AK and Coffey DS. . 1997 Biochem. 62: 1323–1331.
Melek M and Shippen DE. . 1996 Bioessays 18: 301–308.
Nawaz S, Hashizumi TL, Markham NE, Shroyer AL and Shoyer KR. . 1997 Am. J. Clin. Pathol. 107: 542–547.
Nelson NJ. . 1996 J. Natl. Cancer Inst. 88: 1021–1023.
Oshimura M and Barrett JC. . 1997 Eur. J. Cancer 33,: 710–715.
Page DL, Jensen RA and Simpson JF. . 1998 Mod. Pathol. 11: 120–128.
Piatyszek MA, Kim NW, Weinrich SL, Hiyama K, Wright WE and Shay JW. . 1995 Methods Cell Sci. 17: 1–15.
Poremba C, Bocker W, Willenbring H, Schafer KL, Otterbach F, Burger H, Diallo R and Dockhorn-Dworniczak B. . 1998 Int. J. Oncol. 12: 641–648.
Sambrook J, Fritsch EF and Maniatis T. . 1989 In: Molecular Cloning: A Laboratory Manual (2nd edition) Cold Spring Harbour Laboratory Press, Cold Spring Harbour, N.Y.
Shay JW. . 1995 Molec. Med. Today 1: 378–384.
Shay JW and Bacchetti S. . 1997 Eur. J. Cancer 33: 787–791.
Smith JR and Pereira-Smith OM. . 1996 Science 273: 63–67.
Sugino T, Yoshida K, Bolodeoku J, Tahara H, Buley I, Manek S, Wells C, Goodison S, Ide T, Suzuki T, Tahara E and Tarin D. . 1996 Intern. J. Cancer 69: 301–306.
Tsao J, Zhao Y, Lukas J, Yang X, Shah A, Press M and Shibata D. . 1997 Clin. Cancer Res. 3: 627–631.
Umbricht CB, Saji M, Westra WH, Udelsman R, Zeiger, MA and Sukumar S. . 1997 Cancer Res. 57: 2144–2147.
Wright WE and Shay JW. . 1995 Trends Cell Biol. 5: 293–297.
Yashima K, Milchgrub S, Gollahon LS, Maitra A, Saboorian MH, Shay JW and Gazdar AF. . 1998 Clin. Cancer Res. 4: 229–234.
Zhuang A, Bertheau P, Emmert-Buck MR, Liotta LA, Gnarra J, Linehan WM and Lubensky IA. . 1995a Am. J. Pathol. 146: 620–625.
Zhuang Z, Merino MJ, Chuaqui R, Liotta LA and Emmert-Buck MR. . 1995b Cancer Res. 55: 467–471.
Acknowledgements
This study was supported in part by United States Army Medical Research Grant DAMD17-96-6236 to S Sukumar and by Grant #9610 from the Susan G Komen Foundation to CB Umbricht.
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Umbricht, C., Sherman, M., Dome, J. et al. Telomerase activity in ductal carcinoma in situ and invasive breast cancer. Oncogene 18, 3407–3414 (1999). https://doi.org/10.1038/sj.onc.1202714
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DOI: https://doi.org/10.1038/sj.onc.1202714
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