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p53Val135 temperature sensitive mutant suppresses growth of human breast cancer cells (1994)

Eliyahu, Daniel ; Evans, Steve ; Rosen, Neal ; [et al.]

Springer

Breast cancer research and treatment 30 (1994), S. 167-177

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ISSN: 1573-7217

Keywords: breast cancer ; oncogenes ; p53 transformation ; temperature sensitive mutant ; tumor suppressors

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Summary One common step in the malignant progression of a wide variety of human cancers seems to be inactivation of the p53 gene, via point mutation or deletion or both; or overexpression of mutated protein with dominant transforming activity. This study shows a suppressive effect of wild type p53 on the growth of human breast cancer cells. Introduction of wild type p53 versus mutant into five human breast cancer cell lines containing mutant p53 resulted in a marked reduction in colony formation. Two of these were transfected with human wt p53 expression vectors and the other three were infected with retroviruses packaging human wt p53, both showing similar reduction in the number of surviving colonies, suggesting a role for wt p53 in suppression of breast cancer cell growth. Direct evidence for growth suppression was obtained by introduction of the temperature sensitive p53Val135 into Hs578T human breast cancer cells containing a mutant p53. This murine mutant allele p53Val135 functions as an oncogene at 37° C and as a tumor suppressor at 32° C. The cell line generated was strongly growth inhibited at the restrictive temperature (31.5° C), at which temperature the suppressor form is expressed. This inhibition of proliferation was reversible upon a temperature upshift. Analysis of the cell cycle distribution shows these growth suppressed cells to be inhibited in the G1 phase of the cell cycle. Thus wt p53 may have an important role in breast cancer tumorigenesis.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00666061

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Growth regulation of human breast carcinoma occurs through regulated growth factor secretion (1987)

Lippman, Marc E. ; Dickson, Robert B. ; Gelmann, Edward P. ; [et al.]

New York, N.Y. : Wiley-Blackwell

Journal of Cellular Biochemistry 35 (1987), S. 1-16

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ISSN: 0730-2312

Keywords: breast cancer ; growth factors ; estrogen ; IGF-I ; TGF ; PDGF ; Life and Medical Sciences ; Cell & Developmental Biology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Chemistry and Pharmacology , Medicine

Notes: We describe studies on human breast cancer in which it is shown that specific growth factors (IGF-I, TGFα, PDGF) are secreted by human breast cancer cells and likely to be involved in tumor growth and progression. These activities are regulated by estradiol in hormone-dependent breast cancer and secreted constitutively by hormone-independent cells. These growth factor activities can induce the growth of hormone-dependent cells in vivo in athymic nude mice. Hormone-dependent breast cancer cells also secrete TGFβ, a growth-inhibitory substance, when treated with antiestrogens. TGFβ functions as a negative autocrine growth regulator and is responsible for some of the growth-inhibitory effects of antiestrogens.