p53 and bcl-2 immunohistochemical alterations in prostate cancer treated with radiation therapy

Huang, Andrew H.; Gandour‐Edwards, Regina; Rosenthal, Seth A.; Siders, Douglas B.; Deitch, Arline D.; White, Ralph W. deVere

doi:10.1016/s0090-4295(97)00636-5

Cited by 66 publications

(28 citation statements)

References 17 publications

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“…[1][2][3][4][5][6][7] 10 We demonstrated in a case-control study that patients in whom radiotherapy alone fails to control localized prostate cancer have decreased expression of PTEN and overexpression of phosphor-Akt in their cancers. Previously, researchers have demonstrated PTEN expression to potentiate the cytotoxicity effects of chemotherapeutic agents 8 or irradiation.…”

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confidence: 99%

Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation

et al. 2004

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Bcl-2 is associated with resistance to radiotherapy in prostate cancer. It was recently demonstrated that transduction of LNCaP prostate cells with the PTEN gene resulted in Bcl-2 downregulation. We hypothesized that forced expression of PTEN in prostate cancer cells would sensitize cells to radiation, downregulate Bcl-2 expression, and potentiate the G2M block induced by radiation. Four cell lines -PC-3-Bcl-2 (Bcl-2 overexpression, deleted PTEN), PC-3-Neo (wild-type Bcl-2, deleted PTEN), LNCaP (Bcl-2 overexpression, deleted PTEN), and DU-145 (wild-type Bcl-2 and PTEN) -were transduced with a recombinant adenovirus-5 vector expressing the human wild-type PTEN cDNA under the control of a human cytomegalovirus promoter (Ad-MMAC). After correction for the effect of Ad-MMAC on plating efficiency, Ad-MMAC treatment reduced the surviving fractions after 2 Gy as follows: PC-3-Bcl-2, from 60.5 to 3.6%; PC-3-Neo, no reduction; LNCaP, from 29.6 to 16.3%; and DU-145, from 32.7 to 25.7%. PTEN expression was associated with the downregulation of Bcl-2 expression in PC-3-Bcl-2 and LNCaP cell lines. Ad-MMAC plus radiotherapy potentiated the G2M block seen with radiotherapy alone only in PC-3-Bcl-2 cells. These findings suggest that overexpression of Bcl-2 result in radioresistance and inability of radiation to cause its typical G2M cell-cycle arrest.

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Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation

et al. 2004

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“…Degenerative conditions, such as Alzheimer's disease and AIDS, occur in the setting of excess apoptosis, whereas hyperplastic diseases, including cancer, often occur when apoptosis is attenuated (2). Specifically, inhibition of apoptosis rather than enhanced cellular proliferation is the more critical pathophysiological insult that contributes to the development of prostatic adenocarcinoma (CaP) 1 (3,4). CaP is the most commonly diagnosed malignancy in American men and is the second most common cause of death due to cancer, with estimates that 37,000 men died from CaP in 1999 (5).…”

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confidence: 99%

“…For example, the endoplasmic reticulum (ER) serves as an intracellular Ca 2ϩ store that is released into the cytosol in response to a variety of stimuli, including binding of inositol 1,4,5-trisphosphate (IP 3 ) to its cognate ER-localized receptor (IP 3 R) (11). The release of ER Ca 2ϩ stores in turn induces a Ca 2ϩ influx across the plasma membrane, also known as the Ca 2ϩ release-activated Ca 2ϩ current (I CRAC ) (12).…”

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Characterization of Calcium Release-activated Apoptosis of LNCaP Prostate Cancer Cells

Wertz¹,

Dixit²

2000

Journal of Biological Chemistry

117

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Apoptosis inhibition rather than enhanced cellular proliferation occurs in prostate cancer (CaP), the most commonly diagnosed malignancy in American men. Therefore, it is important to characterize residual apoptotic pathways in CaP cells. When Apoptosis is the physiological counterbalance to mitosis and a fundamental mechanism for achieving tissue homeostasis (1). Accordingly, disorders of apoptosis contribute to a number of disease states. Degenerative conditions, such as Alzheimer's disease and AIDS, occur in the setting of excess apoptosis, whereas hyperplastic diseases, including cancer, often occur when apoptosis is attenuated (2). Specifically, inhibition of apoptosis rather than enhanced cellular proliferation is the more critical pathophysiological insult that contributes to the development of prostatic adenocarcinoma (CaP) 1 (3, 4). CaP is the most commonly diagnosed malignancy in American men and is the second most common cause of death due to cancer, with estimates that 37,000 men died from CaP in 1999 (5). Successful CaP therapies have been shown to induce tumor regression via apoptosis; however, therapy-resistant cells fail to die in response to treatment (6). It is therefore important to characterize the residual functional apoptotic pathways in therapy-resistant CaP cells. Perturbation of calcium ion (Ca 2ϩ ) homeostasis is a common occurrence in CaP cells induced to undergo apoptosis by a variety of agents, including chemotherapeutics (7) and androgen ablation (8,9).Although the influx of Ca 2ϩ across the cell membrane results in a dramatic increase in cytosolic [Ca 2ϩ ], this influx is often invoked by a less readily detectable cytosolic [Ca 2ϩ ] elevation as a consequence of organellar Ca 2ϩ store release (10). For example, the endoplasmic reticulum (ER) serves as an intracellular Ca 2ϩ store that is released into the cytosol in response to a variety of stimuli, including binding of inositol 1,4,5-trisphosphate (IP 3 ) to its cognate ER-localized receptor (IP 3 R) (11). The release of ER Ca 2ϩ stores in turn induces a Ca 2ϩ influx across the plasma membrane, also known as the Ca 2ϩ release-activated Ca 2ϩ current (I CRAC ) (12). Thus, the release of ER Ca 2ϩ stores serves to trigger a larger perturbation in cytosolic [Ca 2ϩ ]. Studies with an IP 3 R-deficient Jurkat T-lymphocyte cell line underscore the importance of ER Ca 2ϩ stores in cellular signaling. In contrast to the parental cell line, these cells are defective in antigen-specific T-cell signaling and are resistant to multiple inducers of apoptosis, including Fas ligand, CD3 antibody, glucocorticoids, and irradiation (13). These results are of interest because Jurkat cells have been used to study the role of caspases in apoptosis. Caspases are aspartate-specific cysteine proteases that constitute the effector arm of cell death (14). Upon receipt of an apoptotic stimulus, large pro-domain initiator caspases (such as caspase-8 and -9) are activated by autoproteolysis, which converts the single polypeptide zymogen to form the activ...

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“…Alterations in the p53 gene may play a role in the development of radiation resistance. Despite the conflict in the data, genetic alteration in p53 can be used as a pretreatment marker in predicting local treatment failure with ionising radiation therapy 68,[87][88][89] . Induction of p53 protein after radiation shows specific dependence on cell type of prostate tissue.…”

Section: The Significance Of Key Regulators Of Apoptosis In the Develmentioning

confidence: 99%

The Significance of Key Regulators of Apoptosis in the Development and Prognosis of Prostate Carcinoma. I. Proteins of the BCL-2 Family and Protein P53

Knillová¹,

Kolář²

2003

BIOMED PAP

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p53 and bcl-2 immunohistochemical alterations in prostate cancer treated with radiation therapy

Cited by 66 publications

References 17 publications

Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation

Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation

Characterization of Calcium Release-activated Apoptosis of LNCaP Prostate Cancer Cells

The Significance of Key Regulators of Apoptosis in the Development and Prognosis of Prostate Carcinoma. I. Proteins of the BCL-2 Family and Protein P53

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