Ras-related TC21 is Activated by Mutation in a Breast Cancer Cell Line, but Infrequently in Breast Carcinomas in Vivo

Overview

Journal Br J Cancer

Specialty Oncology

Date 1998 Aug 14

PMID 9703274

Citations 16

Authors

K T Barker

M R Crompton

Affiliations

Soon will be listed here.

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.

Citing Articles

Unmutated RRAS2 emerges as a key oncogene in post-partum-associated triple negative breast cancer.

Cifuentes C, Oeste C, Fernandez-Pisonero I, Hortal A, Garcia-Macias C, Hochart J Mol Cancer. 2024; 23(1):142.

PMID: 38987766 PMC: 11234613. DOI: 10.1186/s12943-024-02054-3.

Characterization of mutant versions of the R-RAS2/TC21 GTPase found in tumors.

Clavain L, Fernandez-Pisonero I, Movilla N, Lorenzo-Martin L, Nieto B, Abad A Oncogene. 2022; 42(5):389-405.

PMID: 36476833 PMC: 9883167. DOI: 10.1038/s41388-022-02563-9.

R-Ras subfamily proteins elicit distinct physiologic effects and phosphoproteome alterations in neurofibromin-null MPNST cells.

Weber S, Brossier N, Prechtl A, Barnes S, Wilson L, Brosius S Cell Commun Signal. 2021; 19(1):95.

PMID: 34530870 PMC: 8447793. DOI: 10.1186/s12964-021-00773-4.

The Role of R-Ras Proteins in Normal and Pathologic Migration and Morphologic Change.

Weber S, Carroll S Am J Pathol. 2021; 191(9):1499-1510.

PMID: 34111428 PMC: 8420862. DOI: 10.1016/j.ajpath.2021.05.008.

Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.

Chang M, Asthana S, Gao S, Lee B, Chapman J, Kandoth C Nat Biotechnol. 2015; 34(2):155-63.

PMID: 26619011 PMC: 4744099. DOI: 10.1038/nbt.3391.

References

Watson D, Elton R, Jack W, Dixon J, Chetty U, Miller W . The H-ras oncogene product p21 and prognosis in human breast cancer. Breast Cancer Res Treat. 1991; 17(3):161-9. DOI: 10.1007/BF01806365. View

Sukumar S . An experimental analysis of cancer: role of ras oncogenes in multistep carcinogenesis. Cancer Cells. 1990; 2(7):199-204. View

Mangues R, SEIDMAN I, Gordon J, Pellicer A . Overexpression of the N-ras proto-oncogene, not somatic mutational activation, associated with malignant tumors in transgenic mice. Oncogene. 1992; 7(10):2073-6. View

Andersen L, Fountain J, Gutmann D, Tarle S, Glover T, Dracopoli N . Mutations in the neurofibromatosis 1 gene in sporadic malignant melanoma cell lines. Nat Genet. 1993; 3(2):118-21. DOI: 10.1038/ng0293-118. View

Legius E, Marchuk D, Collins F, Glover T . Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis. Nat Genet. 1993; 3(2):122-6. DOI: 10.1038/ng0293-122. View

Willis G, Jennings B, Ball R, New N, Gibson I . Analysis of ras point mutations and human papillomavirus 16 and 18 in cervical carcinomata and their metastases. Gynecol Oncol. 1993; 49(3):359-64. DOI: 10.1006/gyno.1993.1140. View

Zhang P, 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; 9(1):46-56. DOI: 10.1002/mc.2940090109. View

Graham S, Cox A, Drivas G, Rush M, DEustachio P, Der C . Aberrant function of the Ras-related protein TC21/R-Ras2 triggers malignant transformation. Mol Cell Biol. 1994; 14(6):4108-15. PMC: 358776. DOI: 10.1128/mcb.14.6.4108-4115.1994. View

Barker K, Martindale J, Mitchell P, Kamalati T, Page M, Phippard D . Expression patterns of the novel receptor-like tyrosine kinase, DDR, in human breast tumours. Oncogene. 1995; 10(3):569-75. View

10.

Clark G, Der C . Aberrant function of the Ras signal transduction pathway in human breast cancer. Breast Cancer Res Treat. 1995; 35(1):133-44. DOI: 10.1007/BF00694753. View

11.

Wong Y, Chung T, Cheung T, Lam S, Xu Y, Chang A . Frequent ras gene mutations in squamous cell cervical cancer. Cancer Lett. 1995; 95(1-2):29-32. DOI: 10.1016/0304-3835(95)03857-s. View

12.

Clark G, Kinch M, Gilmer T, Burridge K, Der C . Overexpression of the Ras-related TC21/R-Ras2 protein may contribute to the development of human breast cancers. Oncogene. 1996; 12(1):169-76. View

13.

Bollag G, Clapp D, Shih S, Adler F, Zhang Y, Thompson P . Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nat Genet. 1996; 12(2):144-8. DOI: 10.1038/ng0296-144. View

14.

Marais R, Marshall C . Control of the ERK MAP kinase cascade by Ras and Raf. Cancer Surv. 1996; 27:101-25. View

15.

Berchuck A, Carney M . Human ovarian cancer of the surface epithelium. Biochem Pharmacol. 1997; 54(5):541-4. DOI: 10.1016/s0006-2952(97)00061-0. View

16.

SANGER F, Nicklen S, Coulson A . DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977; 74(12):5463-7. PMC: 431765. DOI: 10.1073/pnas.74.12.5463. View

17.

Chirgwin J, Przybyla A, MacDonald R, Rutter W . Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979; 18(24):5294-9. DOI: 10.1021/bi00591a005. View

18.

Bar-Sagi D, Feramisco J . Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation. Cell. 1985; 42(3):841-8. DOI: 10.1016/0092-8674(85)90280-6. View

19.

Noda M, Ko M, Ogura A, Liu D, Amano T, Takano T . Sarcoma viruses carrying ras oncogenes induce differentiation-associated properties in a neuronal cell line. Nature. 1985; 318(6041):73-5. DOI: 10.1038/318073a0. View

20.

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; 49(4):465-75. DOI: 10.1016/0092-8674(87)90449-1. View