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Lack of C/EBP alpha gene expression results in increased DNA synthesis and an increased frequency of immortalization of freshly isolated mice [correction of rat] hepatocytes.
Hepatology. 1998 Feb; 27(2):392-401.Hep

Abstract

The CCAAT/enhancer binding protein alpha (C/EBP alpha) binds to specific promoter sequences and directs transcription of many genes expressed in the liver. Overexpression of C/EBP alpha in established cell lines inhibits cell proliferation. Primary hepatocytes from newborn C/EBP alpha(-/-) mice and normal littermates were used to determine whether the absence of C/EBP alpha increased proliferation and/or transformation of these cells in vitro. DNA synthesis, as measured by bromodeoxyuridine (BrdU) incorporation 24 hours postharvest, was fourfold higher in cells from C/EBP alpha(-/-) pups. Established cell lines were derived from 7 of 8 hepatocyte cultures initiated from null mutants, 4 of 23 cultures from heterozygotes, and 0 of 12 cultures from wild-type animals. C/EBP alpha(-/-) cultures had epithelial morphology, showed bile canaliculi, and expressed albumin messenger RNA (mRNA). When cultured on Matrigel, which promotes differentiation, cell lines derived from C/EBP alpha(-/-) mice formed cords and increased albumin mRNA expression by 1.7- to 3.8-fold. C/EBP alpha(-/-) cell lines exhibited rapid growth and rapid accumulation of chromosomal abnormalities, and were capable of forming nodules when inoculated into the abdominal subcutaneous tissue of nude mice. Our data show that C/EBP alpha is an important regulator of hepatocyte proliferation and participates in the maintenance of the nontransformed hepatic phenotype in vitro.

Authors+Show Affiliations

Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030-2399, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9462636

Citation

Soriano, H E., et al. "Lack of C/EBP Alpha Gene Expression Results in Increased DNA Synthesis and an Increased Frequency of Immortalization of Freshly Isolated Mice [correction of Rat] Hepatocytes." Hepatology (Baltimore, Md.), vol. 27, no. 2, 1998, pp. 392-401.
Soriano HE, Kang DC, Finegold MJ, et al. Lack of C/EBP alpha gene expression results in increased DNA synthesis and an increased frequency of immortalization of freshly isolated mice [correction of rat] hepatocytes. Hepatology. 1998;27(2):392-401.
Soriano, H. E., Kang, D. C., Finegold, M. J., Hicks, M. J., Wang, N. D., Harrison, W., & Darlington, G. J. (1998). Lack of C/EBP alpha gene expression results in increased DNA synthesis and an increased frequency of immortalization of freshly isolated mice [correction of rat] hepatocytes. Hepatology (Baltimore, Md.), 27(2), 392-401.
Soriano HE, et al. Lack of C/EBP Alpha Gene Expression Results in Increased DNA Synthesis and an Increased Frequency of Immortalization of Freshly Isolated Mice [correction of Rat] Hepatocytes. Hepatology. 1998;27(2):392-401. PubMed PMID: 9462636.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lack of C/EBP alpha gene expression results in increased DNA synthesis and an increased frequency of immortalization of freshly isolated mice [correction of rat] hepatocytes. AU - Soriano,H E, AU - Kang,D C, AU - Finegold,M J, AU - Hicks,M J, AU - Wang,N D, AU - Harrison,W, AU - Darlington,G J, PY - 1998/2/14/pubmed PY - 1998/2/14/medline PY - 1998/2/14/entrez SP - 392 EP - 401 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 27 IS - 2 N2 - The CCAAT/enhancer binding protein alpha (C/EBP alpha) binds to specific promoter sequences and directs transcription of many genes expressed in the liver. Overexpression of C/EBP alpha in established cell lines inhibits cell proliferation. Primary hepatocytes from newborn C/EBP alpha(-/-) mice and normal littermates were used to determine whether the absence of C/EBP alpha increased proliferation and/or transformation of these cells in vitro. DNA synthesis, as measured by bromodeoxyuridine (BrdU) incorporation 24 hours postharvest, was fourfold higher in cells from C/EBP alpha(-/-) pups. Established cell lines were derived from 7 of 8 hepatocyte cultures initiated from null mutants, 4 of 23 cultures from heterozygotes, and 0 of 12 cultures from wild-type animals. C/EBP alpha(-/-) cultures had epithelial morphology, showed bile canaliculi, and expressed albumin messenger RNA (mRNA). When cultured on Matrigel, which promotes differentiation, cell lines derived from C/EBP alpha(-/-) mice formed cords and increased albumin mRNA expression by 1.7- to 3.8-fold. C/EBP alpha(-/-) cell lines exhibited rapid growth and rapid accumulation of chromosomal abnormalities, and were capable of forming nodules when inoculated into the abdominal subcutaneous tissue of nude mice. Our data show that C/EBP alpha is an important regulator of hepatocyte proliferation and participates in the maintenance of the nontransformed hepatic phenotype in vitro. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/9462636/Lack_of_C/EBP_alpha_gene_expression_results_in_increased_DNA_synthesis_and_an_increased_frequency_of_immortalization_of_freshly_isolated_mice_[correction_of_rat]_hepatocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0270913998000597 DB - PRIME DP - Unbound Medicine ER -