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. 1998 Aug;78(3):296–300. doi: 10.1038/bjc.1998.490

Ras-related TC21 is activated by mutation in a breast cancer cell line, but infrequently in breast carcinomas in vivo.

K T Barker 1, M R Crompton 1
PMCID: PMC2063018  PMID: 9703274

Abstract

Activating ras mutations are found in many types of human tumour. Mutations in Harvey (H-), Kirsten (K-) and neuronal (N-) ras are, however, rarely found in breast carcinomas. TC21 is a ras family member that shares close homology to H-, K- and N-ras, and activating mutations have been found in ovarian carcinoma and leiomyosarcoma cell lines. We have examined panels of cDNAs from breast, ovarian and cervical cell lines, and primary and metastatic breast tumours for mutations in TC21 using a single-strand conformational polymorphism (SSCP)-based assay. One breast cancer cell line, CAL51, exhibited an altered SSCP pattern, compared with normal tissue, which was due to an A-T base change in codon 72, causing a predicted Gln-Leu activating mutation. Of nine primary and 15 metastatic breast tumour cDNAs analysed, none exhibited an altered pattern by SSCP. The apparently wild-type pattern by SSCP analysis was confirmed by sequence analysis of some of the cDNAs assayed. Thus, we conclude that mutations in TC21 are uncommon in breast carcinomas.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersen L. B., Fountain J. W., Gutmann D. H., Tarlé S. A., Glover T. W., Dracopoli N. C., Housman D. E., Collins F. S. Mutations in the neurofibromatosis 1 gene in sporadic malignant melanoma cell lines. Nat Genet. 1993 Feb;3(2):118–121. doi: 10.1038/ng0293-118. [DOI] [PubMed] [Google Scholar]
  2. Bar-Sagi D., Feramisco J. R. Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation. Cell. 1985 Oct;42(3):841–848. doi: 10.1016/0092-8674(85)90280-6. [DOI] [PubMed] [Google Scholar]
  3. Barker K. T., Martindale J. E., Mitchell P. J., Kamalati T., Page M. J., Phippard D. J., Dale T. C., Gusterson B. A., Crompton M. R. Expression patterns of the novel receptor-like tyrosine kinase, DDR, in human breast tumours. Oncogene. 1995 Feb 2;10(3):569–575. [PubMed] [Google Scholar]
  4. Berchuck A., Carney M. Human ovarian cancer of the surface epithelium. Biochem Pharmacol. 1997 Sep 1;54(5):541–544. doi: 10.1016/s0006-2952(97)00061-0. [DOI] [PubMed] [Google Scholar]
  5. Bollag G., Clapp D. W., Shih S., Adler F., Zhang Y. Y., Thompson P., Lange B. J., Freedman M. H., McCormick F., Jacks T. Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nat Genet. 1996 Feb;12(2):144–148. doi: 10.1038/ng0296-144. [DOI] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Clark G. J., Der C. J. Aberrant function of the Ras signal transduction pathway in human breast cancer. Breast Cancer Res Treat. 1995 Jul;35(1):133–144. doi: 10.1007/BF00694753. [DOI] [PubMed] [Google Scholar]
  8. Clark G. J., Kinch M. S., Gilmer T. M., Burridge K., Der C. J. Overexpression of the Ras-related TC21/R-Ras2 protein may contribute to the development of human breast cancers. Oncogene. 1996 Jan 4;12(1):169–176. [PubMed] [Google Scholar]
  9. Drivas G. T., Shih A., Coutavas E., Rush M. G., D'Eustachio P. Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line. Mol Cell Biol. 1990 Apr;10(4):1793–1798. doi: 10.1128/mcb.10.4.1793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Graham S. M., Cox A. D., Drivas G., Rush M. G., D'Eustachio P., Der C. J. Aberrant function of the Ras-related protein TC21/R-Ras2 triggers malignant transformation. Mol Cell Biol. 1994 Jun;14(6):4108–4115. doi: 10.1128/mcb.14.6.4108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Legius E., Marchuk D. A., Collins F. S., Glover T. W. Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis. Nat Genet. 1993 Feb;3(2):122–126. doi: 10.1038/ng0293-122. [DOI] [PubMed] [Google Scholar]
  12. Li Y., Bollag G., Clark R., Stevens J., Conroy L., Fults D., Ward K., Friedman E., Samowitz W., Robertson M. Somatic mutations in the neurofibromatosis 1 gene in human tumors. Cell. 1992 Apr 17;69(2):275–281. doi: 10.1016/0092-8674(92)90408-5. [DOI] [PubMed] [Google Scholar]
  13. Mangues R., Seidman I., Gordon J. W., Pellicer A. Overexpression of the N-ras proto-oncogene, not somatic mutational activation, associated with malignant tumors in transgenic mice. Oncogene. 1992 Oct;7(10):2073–2076. [PubMed] [Google Scholar]
  14. Marais R., Marshall C. J. Control of the ERK MAP kinase cascade by Ras and Raf. Cancer Surv. 1996;27:101–125. [PubMed] [Google Scholar]
  15. Noda M., Ko M., Ogura A., Liu D. G., Amano T., Takano T., Ikawa Y. Sarcoma viruses carrying ras oncogenes induce differentiation-associated properties in a neuronal cell line. Nature. 1985 Nov 7;318(6041):73–75. doi: 10.1038/318073a0. [DOI] [PubMed] [Google Scholar]
  16. Riou G., Barrois M., Sheng Z. M., Duvillard P., Lhomme C. Somatic deletions and mutations of c-Ha-ras gene in human cervical cancers. Oncogene. 1988 Sep;3(3):329–333. [PubMed] [Google Scholar]
  17. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sinn E., Muller W., Pattengale P., Tepler I., Wallace R., Leder P. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell. 1987 May 22;49(4):465–475. doi: 10.1016/0092-8674(87)90449-1. [DOI] [PubMed] [Google Scholar]
  19. Sukumar S. An experimental analysis of cancer: role of ras oncogenes in multistep carcinogenesis. Cancer Cells. 1990 Jul;2(7):199–204. [PubMed] [Google Scholar]
  20. Watson D. M., Elton R. A., Jack W. J., Dixon J. M., Chetty U., Miller W. R. The H-ras oncogene product p21 and prognosis in human breast cancer. Breast Cancer Res Treat. 1991 Jan-Feb;17(3):161–169. doi: 10.1007/BF01806365. [DOI] [PubMed] [Google Scholar]
  21. Willis G., Jennings B., Ball R. Y., New N. E., Gibson I. Analysis of ras point mutations and human papillomavirus 16 and 18 in cervical carcinomata and their metastases. Gynecol Oncol. 1993 Jun;49(3):359–364. doi: 10.1006/gyno.1993.1140. [DOI] [PubMed] [Google Scholar]
  22. Wong Y. F., Chung T. K., Cheung T. H., Lam S. K., Xu Y. G., Chang A. M. Frequent ras gene mutations in squamous cell cervical cancer. Cancer Lett. 1995 Aug 16;95(1-2):29–32. doi: 10.1016/0304-3835(95)03857-s. [DOI] [PubMed] [Google Scholar]
  23. Zhang P. L., Calaf G., Russo J. Allele loss and point mutation in codons 12 and 61 of the c-Ha-ras oncogene in carcinogen-transformed human breast epithelial cells. Mol Carcinog. 1994 Jan;9(1):46–56. doi: 10.1002/mc.2940090109. [DOI] [PubMed] [Google Scholar]
  24. van 't Veer L. J., Hermens R., van den Berg-Bakker L. A., Cheng N. C., Fleuren G. J., Bos J. L., Cleton F. J., Schrier P. I. ras oncogene activation in human ovarian carcinoma. Oncogene. 1988 Feb;2(2):157–165. [PubMed] [Google Scholar]

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