Down-regulation of a calmodulin-related gene during transformation of human mammary epithelial cells
- Lawrence Berkeley Laboratory, CA (USA)
- Stanford Univ. Medical Center, CA (USA)
- Dana-Farber Cancer Institute, Boston, MA (USA)
A human cDNA library obtained from cultured normal mammary epithelial cells (HMECs) was searched by subtractive hybridization for genes whose decrease in expression might be relevant to epithelial transformation. One clone identified by this procedure corresponded to a 1.4 kilobase mRNA, designated NB-1, whose expression was decreased >50-fold in HMECs tumorigenically transformed in vitro after exposure to benzo({alpha})pyrene and Kirsten sarcoma virus. Sequence analysis of NB-1 cDNA revealed an open reading frame with a high degree of homology to calmodulin. NB-1 expression could be demonstrated by polymerase chain reaction amplification in normal breast, prostate, cervix, and epidermal tissues. The presence of NB-1 transcripts was variable in primary breast carcinoma tissues and undetectable in tumor-derived cell lines of breast, prostate, or other origins. NB-1 mRNA expression could be down-regulated in cultured HMECs by exposure to reconstituted extracellular matrix material, while exposure to transforming growth factor type {beta} increased its relative abundance. The protein encoded by NB-1 may have Ca{sup 2{sup plus}} binding properties and perform functions similar to those of authentic calmodulin. Its possible roles in differentiation and/or suppression of tumorigenicity in epithelial tissues remain to be examined.
- DOE Contract Number:
- AC03-76SF00098
- OSTI ID:
- 5546952
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:19; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CALMODULIN
GENE REGULATION
EPITHELIUM
ONCOGENIC TRANSFORMATIONS
RECOMBINANT DNA
DNA SEQUENCING
BENZOPYRENE
CARCINOMAS
CELL DIFFERENTIATION
DNA HYBRIDIZATION
GENES
MAMMARY GLANDS
ONCOGENIC VIRUSES
SARCOMAS
ANIMAL TISSUES
AROMATICS
BODY
CELL TRANSFORMATIONS
CONDENSED AROMATICS
DISEASES
DNA
GLANDS
HYBRIDIZATION
HYDROCARBONS
MICROORGANISMS
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PARASITES
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
TISSUES
VIRUSES
550201* - Biochemistry- Tracer Techniques