Expression of the gene coding for a human mucin in mouse mammary tumor cells can affect their tumorigenicity

El Nasir Lalani, Feodor Berdichevsky, Martina Boshell, Moira Shearer, David Wilson, Hans Status, Sandra J Gendler, Joyce Taylor-Papadimitriou

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The human epithelial mucin which is the product of the MUC1 gene is expressed by many carcinomas, including those of breast, ovary, colon, and lung. The core protein is aberrantly glycosylated in the tumors resulting in the exposure or appearance of novel epitopes. To examine the possibility of using the MUC1 gene and its products in active immunization against breast and other carcinomas, we have developed a syngeneic mouse model, by transfecting the gene into the mouse mammary epithelial tumor cell 410.4. An 8.3-kilobase EcoRI fragment of the gene was transfected using the expression vector pEMSV scribe α2. Transcripts of the correct size, initiating from the transcriptional start site seen in human cells, were observed in the transfectants. The mucin was expressed in the cytoplasm and in the membrane, and the glycosylation pattern appeared to be similar to that seen in human tumor cells, since the core protein epitopes recognized by antibodies HMFG-1, HMFG-2, and SM-3 were exposed. The 410.4 transfectants expressing the human mucin showed a reduction in tumor incidence at low inocula and a delay in tumor growth at higher inocula. Pretreatment with 104 transfected cells could inhibit the development of tumors from a subsequent inoculum of 106 transfectants, but had no effect on the tumor development of the untransfected 410.4 cells. Our results suggest that the human mucin expressed by the 410.4 cells may mobilize an immune response which inhibits tumor development. They also indicate that the mouse model will be useful for evaluation of efficacy of immunogens based on the MUC1 gene and its product.

Original languageEnglish (US)
Pages (from-to)15420-15426
Number of pages7
JournalJournal of Biological Chemistry
Volume266
Issue number23
StatePublished - 1991
Externally publishedYes

Fingerprint

Mucins
Tumors
Genes
Cells
Breast Neoplasms
Gene Expression
Neoplasms
Epitopes
Immunization
Glycosylation
Ovary
Colon
Cytoplasm
Vaccination
Proteins
Breast
Epithelial Cells
Carcinoma
Lung
Membranes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lalani, E. N., Berdichevsky, F., Boshell, M., Shearer, M., Wilson, D., Status, H., ... Taylor-Papadimitriou, J. (1991). Expression of the gene coding for a human mucin in mouse mammary tumor cells can affect their tumorigenicity. Journal of Biological Chemistry, 266(23), 15420-15426.

Expression of the gene coding for a human mucin in mouse mammary tumor cells can affect their tumorigenicity. / Lalani, El Nasir; Berdichevsky, Feodor; Boshell, Martina; Shearer, Moira; Wilson, David; Status, Hans; Gendler, Sandra J; Taylor-Papadimitriou, Joyce.

In: Journal of Biological Chemistry, Vol. 266, No. 23, 1991, p. 15420-15426.

Research output: Contribution to journalArticle

Lalani, EN, Berdichevsky, F, Boshell, M, Shearer, M, Wilson, D, Status, H, Gendler, SJ & Taylor-Papadimitriou, J 1991, 'Expression of the gene coding for a human mucin in mouse mammary tumor cells can affect their tumorigenicity', Journal of Biological Chemistry, vol. 266, no. 23, pp. 15420-15426.
Lalani EN, Berdichevsky F, Boshell M, Shearer M, Wilson D, Status H et al. Expression of the gene coding for a human mucin in mouse mammary tumor cells can affect their tumorigenicity. Journal of Biological Chemistry. 1991;266(23):15420-15426.
Lalani, El Nasir ; Berdichevsky, Feodor ; Boshell, Martina ; Shearer, Moira ; Wilson, David ; Status, Hans ; Gendler, Sandra J ; Taylor-Papadimitriou, Joyce. / Expression of the gene coding for a human mucin in mouse mammary tumor cells can affect their tumorigenicity. In: Journal of Biological Chemistry. 1991 ; Vol. 266, No. 23. pp. 15420-15426.
@article{5bbcd8963cfe472686418017c4c2affa,
title = "Expression of the gene coding for a human mucin in mouse mammary tumor cells can affect their tumorigenicity",
abstract = "The human epithelial mucin which is the product of the MUC1 gene is expressed by many carcinomas, including those of breast, ovary, colon, and lung. The core protein is aberrantly glycosylated in the tumors resulting in the exposure or appearance of novel epitopes. To examine the possibility of using the MUC1 gene and its products in active immunization against breast and other carcinomas, we have developed a syngeneic mouse model, by transfecting the gene into the mouse mammary epithelial tumor cell 410.4. An 8.3-kilobase EcoRI fragment of the gene was transfected using the expression vector pEMSV scribe α2. Transcripts of the correct size, initiating from the transcriptional start site seen in human cells, were observed in the transfectants. The mucin was expressed in the cytoplasm and in the membrane, and the glycosylation pattern appeared to be similar to that seen in human tumor cells, since the core protein epitopes recognized by antibodies HMFG-1, HMFG-2, and SM-3 were exposed. The 410.4 transfectants expressing the human mucin showed a reduction in tumor incidence at low inocula and a delay in tumor growth at higher inocula. Pretreatment with 104 transfected cells could inhibit the development of tumors from a subsequent inoculum of 106 transfectants, but had no effect on the tumor development of the untransfected 410.4 cells. Our results suggest that the human mucin expressed by the 410.4 cells may mobilize an immune response which inhibits tumor development. They also indicate that the mouse model will be useful for evaluation of efficacy of immunogens based on the MUC1 gene and its product.",
author = "Lalani, {El Nasir} and Feodor Berdichevsky and Martina Boshell and Moira Shearer and David Wilson and Hans Status and Gendler, {Sandra J} and Joyce Taylor-Papadimitriou",
year = "1991",
language = "English (US)",
volume = "266",
pages = "15420--15426",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "23",

}

TY - JOUR

T1 - Expression of the gene coding for a human mucin in mouse mammary tumor cells can affect their tumorigenicity

AU - Lalani, El Nasir

AU - Berdichevsky, Feodor

AU - Boshell, Martina

AU - Shearer, Moira

AU - Wilson, David

AU - Status, Hans

AU - Gendler, Sandra J

AU - Taylor-Papadimitriou, Joyce

PY - 1991

Y1 - 1991

N2 - The human epithelial mucin which is the product of the MUC1 gene is expressed by many carcinomas, including those of breast, ovary, colon, and lung. The core protein is aberrantly glycosylated in the tumors resulting in the exposure or appearance of novel epitopes. To examine the possibility of using the MUC1 gene and its products in active immunization against breast and other carcinomas, we have developed a syngeneic mouse model, by transfecting the gene into the mouse mammary epithelial tumor cell 410.4. An 8.3-kilobase EcoRI fragment of the gene was transfected using the expression vector pEMSV scribe α2. Transcripts of the correct size, initiating from the transcriptional start site seen in human cells, were observed in the transfectants. The mucin was expressed in the cytoplasm and in the membrane, and the glycosylation pattern appeared to be similar to that seen in human tumor cells, since the core protein epitopes recognized by antibodies HMFG-1, HMFG-2, and SM-3 were exposed. The 410.4 transfectants expressing the human mucin showed a reduction in tumor incidence at low inocula and a delay in tumor growth at higher inocula. Pretreatment with 104 transfected cells could inhibit the development of tumors from a subsequent inoculum of 106 transfectants, but had no effect on the tumor development of the untransfected 410.4 cells. Our results suggest that the human mucin expressed by the 410.4 cells may mobilize an immune response which inhibits tumor development. They also indicate that the mouse model will be useful for evaluation of efficacy of immunogens based on the MUC1 gene and its product.

AB - The human epithelial mucin which is the product of the MUC1 gene is expressed by many carcinomas, including those of breast, ovary, colon, and lung. The core protein is aberrantly glycosylated in the tumors resulting in the exposure or appearance of novel epitopes. To examine the possibility of using the MUC1 gene and its products in active immunization against breast and other carcinomas, we have developed a syngeneic mouse model, by transfecting the gene into the mouse mammary epithelial tumor cell 410.4. An 8.3-kilobase EcoRI fragment of the gene was transfected using the expression vector pEMSV scribe α2. Transcripts of the correct size, initiating from the transcriptional start site seen in human cells, were observed in the transfectants. The mucin was expressed in the cytoplasm and in the membrane, and the glycosylation pattern appeared to be similar to that seen in human tumor cells, since the core protein epitopes recognized by antibodies HMFG-1, HMFG-2, and SM-3 were exposed. The 410.4 transfectants expressing the human mucin showed a reduction in tumor incidence at low inocula and a delay in tumor growth at higher inocula. Pretreatment with 104 transfected cells could inhibit the development of tumors from a subsequent inoculum of 106 transfectants, but had no effect on the tumor development of the untransfected 410.4 cells. Our results suggest that the human mucin expressed by the 410.4 cells may mobilize an immune response which inhibits tumor development. They also indicate that the mouse model will be useful for evaluation of efficacy of immunogens based on the MUC1 gene and its product.

UR - http://www.scopus.com/inward/record.url?scp=0025916187&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025916187&partnerID=8YFLogxK

M3 - Article

C2 - 1714457

AN - SCOPUS:0025916187

VL - 266

SP - 15420

EP - 15426

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 23

ER -