Extracellular matrix and hormones transcriptionally regulate bovine. beta. -casein 5 prime sequences in stably transfected mouse mammary cells

Journal Article · Sat Dec 01 00:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.23.9118· OSTI ID:6397579

Myers, C A; Casperson, G F ^[1]

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1. Monsanto Corporate Research, St. Louis, MO (United States)

Milk protein regulation involves synergistic action of lactogenic hormones and extracellular matrix (ECM). It is well established that substratum has a dramatic effect on morphology and function of mammary cells. The molecular mechanisms that regulate the ECM- and hormone-dependent gene expression, however, have not been resolved. To address this question, a subpopulation (designated CID 9) of the mouse mammary epithelial cell strain COMMA-2D has been developed in which more than 35% of the cells express {beta}-casein, form alveoli-like structures when plated onto a reconstituted basement membrane, and secrete {beta}-casein undirectionally into a lumen. These cells were stably transfected with a series of chloramphenicol acetyltransferase (CAT) fusion genes to study transcriptional regulation of the bovine {beta}-casein gene. The expression of CAT in these lines demonstrated a striking matrix and hormone dependency. This regulation occurered primarily at the transcriptional level and was dependent on the length of the 5{prime} flanking region of the {beta}-casein promotor. Both matrix and hormonal control of transcription occurred within at least the first 1790 base pairs upstream and/or 42 base pairs downstream of the transcriptional initiation site. The ECM effect was independent of glucocorticoid stimulation. However, prolactin was essential and hydrocortisone further increased CAT expression. Endogenous {beta}-casein expression in these lines was similar to that of the parent CID 9 cells. Our data indicate the existence of matrix-dependent elements that regulate transcription.

• DOE Contract Number: AC03-76SF00098
• OSTI ID: 6397579
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 87:23; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CASEIN
GENE REGULATION
GENE REPRESSORS
TRANSCRIPTION
AMINO ACID SEQUENCE
CATTLE
HYDROCORTISONE
LH
MAMMARY GLANDS
MICE
TRANSFERASES
ADRENAL HORMONES
ANIMALS
BODY
CORTICOSTEROIDS
DOMESTIC ANIMALS
ENZYMES
GLANDS
GLUCOCORTICOIDS
GONADOTROPINS
HORMONES
HYDROXY COMPOUNDS
KETONES
MAMMALS
MOLECULAR STRUCTURE
NUCLEOPROTEINS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PEPTIDE HORMONES
PITUITARY HORMONES
PREGNANES
PROTEINS
RODENTS
RUMINANTS
STEROID HORMONES
STEROIDS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques