Retinoblastoma Function is a Better Indicator of Cellular Phenotype in Cultured Breast Adenocarcinoma Cells than Retinoblastoma Expression

Botos, Jeannine; Smith, Roger; Kochevar, Deborah T.

doi:10.1177/153537020222700508

Cited by 11 publications

(10 citation statements)

References 43 publications

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“…21,22 In the MDA-MB-435 cells, the intact Rb protein is expressed, whereas in the MDA-MB-231 cells, the protein functions abnormally because of a p16 deficiency. 15,23,24 E2F activity assay also supported this conclusion.…”

Section: Combination Of Virotherapy and Trail Gene Therapy W Guo Et Alsupporting

confidence: 63%

“…3,4,15 As the MDA-MB-231 and MDA-MB-435 cells were dramatically different in their susceptibility, we tested Rb status in these two cell lines. The Western blot analysis showed that the Rb proteins in the MDA-MB-231 cells were heavily phosphorylated (Figure 2a), suggesting that Rb was inactivated in this cell line.…”

Section: Combination Of Adenovirotherapy and Trail Gene Therapy Enhanmentioning

confidence: 99%

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Combination effect of oncolytic adenovirotherapy and TRAIL gene therapy in syngeneic murine breast cancer models

et al. 2005

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy and oncolytic adenovirotherapy have been investigated extensively in xenografic human tumor models established in immunocompromised nude mice. However, the effects of these therapies on syngeneic murine tumors in immunocompetent settings were not well documented. We hypothesized that TRAIL gene therapy used with an oncolytic adenovirus would overcome the weaknesses of the two therapies used individually. In this study, we evaluated the antitumor effects of an oncolytic adenovirus, Delta24, in both human and murine breast cancer cell lines. We also analyzed the effects of TRAIL gene therapy combined with oncolytic virotherapy in these cancer cells. Our results showed that Delta24 can replicate and help the E1-deleted adenovector replicate in murine cancer cells. We also found that these two therapies combined had greater antitumor activity than either one alone in both human and murine breast cancer cells lines and in the syngeneic breast cancer models established in immunocompetent mice. Moreover, Delta24 virotherapy alone and combined with TRAIL gene therapy dramatically reduced the spontaneous liver metastasis that originated in the subcutaneous 4T1 tumor established in Balb/c mice. These findings provide important considerations in the development and preclinical assessments of oncolytic virotherapy.

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Section: Combination Of Virotherapy and Trail Gene Therapy W Guo Et Alsupporting

confidence: 63%

Section: Combination Of Adenovirotherapy and Trail Gene Therapy Enhanmentioning

confidence: 99%

Combination effect of oncolytic adenovirotherapy and TRAIL gene therapy in syngeneic murine breast cancer models

et al. 2005

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“…3B). The inconsistency of our finding, whereby no G1-S progression occurred after release from serum deprivation condition with a previous report with MDA-MB-231 cells is not explainable at this time (20). However, we noted an S phase accumulation along with a decrease of cell population at the G2/M phase in response to the treatment.…”

Section: Discussioncontrasting

confidence: 99%

Anti-proliferative and anti-invasive properties of a purified fraction from Streptomyces sp. H7372

Yip

Cheenpracha²,

Chang³

et al. 2010

Int J Oncol

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Abstract. Secondary metabolites from actinomycetes especially the genus Streptomyces may be one of the most important sources for novel anticancer agents. A purified fraction from a novel actinomycete strain, Streptomyces sp. H7372, was elucidated in breast cancer cells. We have isolated three purified fractions from a novel strain, Streptomyces sp. H7372. One of the fractions, designated as 31-2, exhibited the strongest growth-inhibitory effect and thereby was selected for further studies. 31-2 exerted a growth-inhibitory effect on a panel of 15 human cancer and 2 non-malignant cell lines. In MCF-7 and MDA-MB-231 breast cancer cells, 31-2 induced a cytostatic (anti-proliferative) effect without causing cytotoxicity (cell death). Our data suggest that the cytostasis resulted from cell cycle arrest at the G1 phase in MCF-7 cells and at the S phase in MDA-MB-231 cells. Western blot analysis demonstrated a modulation of phosphorylation of the Rb and CDC2 proteins and of CDK4, cyclin D1 and cyclin D3 in the 31-2-treated breast cancer cell lines. The protein levels of CDK2, CDK6, and PCNA were not affected by 31-2 treatment. 31-2 also exhibited an anti-invasive effect in MDA-MB-231 cells. However, this effect is not attributed to the modulation of proteolytic activity in MDA-MB-231 cells as the enzymatic degradation of type IV collagen was not affected by 31-2. The 31-2 is a potent cytostatic and anti-invasive agent and modulates the cell cycle pathway. Together, these results will have important implications in searching for novel approaches to treat cancer.

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“…It is known that dephosphorylation of Rb as well as an increase in p21 levels and an increase in p53 in concert with dephosphorylation of Rb are not enough to allow suppression of E2F activity in the MCF-7 breast tumor cells, suggesting that E2F activity is no longer susceptible to modulation by endogenous p21 or Rb in such cancer cells (24,25). MCF-7 cells also lack p16 Ink4a , which is a tumor suppressor protein that sequesters and inhibits CDK4 and CDK6 (26,27).…”

Section: M44km64e Mutant Azurin Significantly Reduces the Levels Of Imentioning

confidence: 99%

Apoptosis or growth arrest: Modulation of tumor suppressor p53's specificity by bacterial redox protein azurin

Yamada

Hiraoka

Ikehata

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The tumor suppressor protein p53 is known to induce either apoptosis or growth arrest depending on cellular background. We have previously reported that a bacterial redox protein azurin induces apoptosis in J774 cell line-derived macrophages whereas a site-directed mutant M44KM64E azurin shows very little cytotoxicity and fails to induce apoptosis in J774 cells. We now report that purified M44KM64E mutant azurin protein can enter both J774 cells as well as the human breast cancer MCF-7 cells. Entry of M44KM64E mutant azurin in J774 cells causes strong inhibition of cell-cycle progression at the G1 to S phase and a higher level of transcription of the p21 gene. Corresponding to high p21 levels, the levels of cyclins and cyclin-dependent kinases were greatly lowered in M44KM64E mutant azurin-treated J774 cells. Interestingly, M44KM64E mutant azurin protein failed to elicit inhibition of cell-cycle progression in MCF-7 cells, presumably because of mutation at the retinoblastoma tumor suppressor protein that allows functional E2F formation in MCF-7 cells even in the presence of high intracellular p21 level. Thus, the WT azurin induces apoptosis but little inhibition of cell-cycle progression whereas the M44KM64E mutant azurin is deficient in the induction of apoptosis but mediates strong inhibition of cell-cycle progression, demonstrating the role of a single bacterial protein and its hydrophobic patch in modulating two important functions of p53.

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Retinoblastoma Function is a Better Indicator of Cellular Phenotype in Cultured Breast Adenocarcinoma Cells than Retinoblastoma Expression

Cited by 11 publications

References 43 publications

Combination effect of oncolytic adenovirotherapy and TRAIL gene therapy in syngeneic murine breast cancer models

Combination effect of oncolytic adenovirotherapy and TRAIL gene therapy in syngeneic murine breast cancer models

Anti-proliferative and anti-invasive properties of a purified fraction from Streptomyces sp. H7372

Apoptosis or growth arrest: Modulation of tumor suppressor p53's specificity by bacterial redox protein azurin

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