Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer

Jenny L C Lin, Xin Geng, Sangeeta Das Bhattacharya, JaeRan Yu, Rebecca S. Reiter, Bhagyalakshmi Sastri, Kenneth D. Glazier, Zafar K. Mirza, Kenneth Ke Ning Wang, Peter S. Amenta, Kiron M. Das, Jim J C Lin

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Nonmuscle human tropomyosin (hTM) isoforms have distinct functions and may play important roles in various disease processes. Methods: In an attempt to identify colon epithelial tropomyosin isoform, a complementary DNA library prepared from a human colon cancer cell line T84 was screened by an oligonucleotide probe complementary to messages of all known hTM isoforms. A novel clone called TC22 was obtained. The amino acid sequence of TC22 isoform is identical to isoform 5 (hTM5) apart from the C terminal domain, amino acids 222-247 coding the exon 9. Results: Northern blot analysis showed that TC22 message is expressed in transformed epithelial cell lines and tumor tissues but not in normal epithelial cells. We developed a monoclonal antibody specific to TC22 isoform (TC22-4). By Western blot and immunoperoxidase assays, we analyzed 105 colonic specimens (fresh frozen and formalin fixed) from 96 patients with colon polyps (hyperplastic) or adenomas with or without dysplasia and cancer. Twenty-one of 22 (95%) of colon cancer specimens showed the presence of TC22, compared with only 1 of the 17 normal colon specimens and none of the 13 hyperplastic polyps (P < 0.0001). As assayed by immunoperoxidase staining, TC22 expression progressively increased in benign adenomatous polyps (35%) and polyps with mild and severe dysplasia (57% and 100%, respectively). Conclusions: We cloned and sequenced a novel hTM isoform, TC22, which is strongly associated with colonic neoplasia and carcinoma. TC22 may provide a useful biomarker for surveillance of colon cancer.

Original languageEnglish (US)
Pages (from-to)152-162
Number of pages11
JournalGastroenterology
Volume123
Issue number1
DOIs
StatePublished - 2002

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Tropomyosin
Colonic Neoplasms
Protein Isoforms
Polyps
Colon
Epithelial Cells
Adenomatous Polyps
Neoplasms
Transformed Cell Line
Oligonucleotide Probes
Gene Library
Northern Blotting
Adenoma
Formaldehyde
Amino Acid Sequence
Exons
Complementary DNA
Clone Cells
Biomarkers
Western Blotting

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Lin, J. L. C., Geng, X., Bhattacharya, S. D., Yu, J., Reiter, R. S., Sastri, B., ... Lin, J. J. C. (2002). Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer. Gastroenterology, 123(1), 152-162. https://doi.org/10.1053/gast.2002.34154

Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer. / Lin, Jenny L C; Geng, Xin; Bhattacharya, Sangeeta Das; Yu, JaeRan; Reiter, Rebecca S.; Sastri, Bhagyalakshmi; Glazier, Kenneth D.; Mirza, Zafar K.; Wang, Kenneth Ke Ning; Amenta, Peter S.; Das, Kiron M.; Lin, Jim J C.

In: Gastroenterology, Vol. 123, No. 1, 2002, p. 152-162.

Research output: Contribution to journalArticle

Lin, JLC, Geng, X, Bhattacharya, SD, Yu, J, Reiter, RS, Sastri, B, Glazier, KD, Mirza, ZK, Wang, KKN, Amenta, PS, Das, KM & Lin, JJC 2002, 'Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer', Gastroenterology, vol. 123, no. 1, pp. 152-162. https://doi.org/10.1053/gast.2002.34154
Lin, Jenny L C ; Geng, Xin ; Bhattacharya, Sangeeta Das ; Yu, JaeRan ; Reiter, Rebecca S. ; Sastri, Bhagyalakshmi ; Glazier, Kenneth D. ; Mirza, Zafar K. ; Wang, Kenneth Ke Ning ; Amenta, Peter S. ; Das, Kiron M. ; Lin, Jim J C. / Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer. In: Gastroenterology. 2002 ; Vol. 123, No. 1. pp. 152-162.
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abstract = "Background & Aims: Nonmuscle human tropomyosin (hTM) isoforms have distinct functions and may play important roles in various disease processes. Methods: In an attempt to identify colon epithelial tropomyosin isoform, a complementary DNA library prepared from a human colon cancer cell line T84 was screened by an oligonucleotide probe complementary to messages of all known hTM isoforms. A novel clone called TC22 was obtained. The amino acid sequence of TC22 isoform is identical to isoform 5 (hTM5) apart from the C terminal domain, amino acids 222-247 coding the exon 9. Results: Northern blot analysis showed that TC22 message is expressed in transformed epithelial cell lines and tumor tissues but not in normal epithelial cells. We developed a monoclonal antibody specific to TC22 isoform (TC22-4). By Western blot and immunoperoxidase assays, we analyzed 105 colonic specimens (fresh frozen and formalin fixed) from 96 patients with colon polyps (hyperplastic) or adenomas with or without dysplasia and cancer. Twenty-one of 22 (95{\%}) of colon cancer specimens showed the presence of TC22, compared with only 1 of the 17 normal colon specimens and none of the 13 hyperplastic polyps (P < 0.0001). As assayed by immunoperoxidase staining, TC22 expression progressively increased in benign adenomatous polyps (35{\%}) and polyps with mild and severe dysplasia (57{\%} and 100{\%}, respectively). Conclusions: We cloned and sequenced a novel hTM isoform, TC22, which is strongly associated with colonic neoplasia and carcinoma. TC22 may provide a useful biomarker for surveillance of colon cancer.",
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AU - Geng, Xin

AU - Bhattacharya, Sangeeta Das

AU - Yu, JaeRan

AU - Reiter, Rebecca S.

AU - Sastri, Bhagyalakshmi

AU - Glazier, Kenneth D.

AU - Mirza, Zafar K.

AU - Wang, Kenneth Ke Ning

AU - Amenta, Peter S.

AU - Das, Kiron M.

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