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Prognostic value of LINE-1 retrotransposon expression and its subcellular localization in breast cancer.

Chen L, Dahlstrom JE, Chandra A, Board P, Rangasamy D - Breast Cancer Res. Treat. (2012)

Bottom Line: The majority of invasive cancers were found to express both ORF1p and ORF2p in the cytoplasm, while nuclear expression was also seen in a subclass of those invasive cancers in the range of 28-31 %.Tumors with high nuclear expression of ORF1p and ORF2p were more significantly associated with lymph node metastasis (p = 0.001) and the worst patient survival (p < 0.0001) than those with cytoplasmic expression.Our observation shows altered expression patterns of ORF1p and ORF2p within invasive cancers, which are related to differences in overall patient survival.

View Article: PubMed Central - PubMed

Affiliation: John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia.

ABSTRACT
Long interspersed nuclear element 1 (L1) belongs to a family of retrotransposons. Expression of the normally repressed L1 retrotransposons has been shown to induce genome instability by creating DNA double-stranded breaks and chromosomal rearrangements through the process of retrotransposition. At present, little is known about the expression of L1-encoded ORF1p and ORF2p which are indispensable for its retrotransposition activity. Given its potentially harmful effects on the genome, we investigated the implications of both ORF1p and ORF2p expression and their subcellular localization in a range of breast cancer cell lines and breast tumor tissues including 15 normal breast tissues, 25 fibroadenomas, 25 ductal carcinomas in situ (DCIS), and 95 invasive cancers. Clinicopathologic parameters and survival outcomes were investigated in association with the cytoplasmic and nuclear expression of ORF1p and ORF2p using univariate and multivariate analysis. High cytoplasmic expression of ORF1p and ORF2p was seen in DCIS tumors, but they were not related with survival outcome. The majority of invasive cancers were found to express both ORF1p and ORF2p in the cytoplasm, while nuclear expression was also seen in a subclass of those invasive cancers in the range of 28-31 %. Tumors with high nuclear expression of ORF1p and ORF2p were more significantly associated with lymph node metastasis (p = 0.001) and the worst patient survival (p < 0.0001) than those with cytoplasmic expression. This is the first study examining the effects of both ORF1p and ORF2p expression in breast cancer tissues. Our observation shows altered expression patterns of ORF1p and ORF2p within invasive cancers, which are related to differences in overall patient survival. The differing patterns of both cytoplasmic and nuclear ORF1p and ORF2p expression indicate that further studies of the biology and function of L1 retrotransposons are required in breast cancer.

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Related in: MedlinePlus

Immunohistochemistry of ORF1p and ORF2p in patient’s tumor tissues. Shown is representative immunohistochemistry of ORF1p (top panel) and ORF2p (bottom panel) expressions. A higher magnification of insert is shown below. A, D In normal breast; B, E showing high cytoplasmic expression in DCIS; and C, F both nuclear and cytoplasmic expressions of ORF1p and ORF2p. Bar represents 200-μm scale. Hematoxylin (blue) represents the nuclei of cells and pink highlights ORF1p and ORF2p
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Fig3: Immunohistochemistry of ORF1p and ORF2p in patient’s tumor tissues. Shown is representative immunohistochemistry of ORF1p (top panel) and ORF2p (bottom panel) expressions. A higher magnification of insert is shown below. A, D In normal breast; B, E showing high cytoplasmic expression in DCIS; and C, F both nuclear and cytoplasmic expressions of ORF1p and ORF2p. Bar represents 200-μm scale. Hematoxylin (blue) represents the nuclei of cells and pink highlights ORF1p and ORF2p

Mentions: To evaluate a potential link between expression of ORF1p and ORF2p and the various stages of breast cancer, we screened paraffin-embedded breast tumor tissues by immunohistochemistry (Fig. 3). There was little or no expression in normal breast tissues (n = 15). In contrast, both ORF1p and ORF2p were differentially expressed in the breast tumors, and expressions were higher and more intense staining in DCIS than in invasive cancers. Table 1 shows the overall presence or the absence of the ORF1p and ORF2p expression regardless of location.Fig. 3


Prognostic value of LINE-1 retrotransposon expression and its subcellular localization in breast cancer.

Chen L, Dahlstrom JE, Chandra A, Board P, Rangasamy D - Breast Cancer Res. Treat. (2012)

Immunohistochemistry of ORF1p and ORF2p in patient’s tumor tissues. Shown is representative immunohistochemistry of ORF1p (top panel) and ORF2p (bottom panel) expressions. A higher magnification of insert is shown below. A, D In normal breast; B, E showing high cytoplasmic expression in DCIS; and C, F both nuclear and cytoplasmic expressions of ORF1p and ORF2p. Bar represents 200-μm scale. Hematoxylin (blue) represents the nuclei of cells and pink highlights ORF1p and ORF2p
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3473189&req=5

Fig3: Immunohistochemistry of ORF1p and ORF2p in patient’s tumor tissues. Shown is representative immunohistochemistry of ORF1p (top panel) and ORF2p (bottom panel) expressions. A higher magnification of insert is shown below. A, D In normal breast; B, E showing high cytoplasmic expression in DCIS; and C, F both nuclear and cytoplasmic expressions of ORF1p and ORF2p. Bar represents 200-μm scale. Hematoxylin (blue) represents the nuclei of cells and pink highlights ORF1p and ORF2p
Mentions: To evaluate a potential link between expression of ORF1p and ORF2p and the various stages of breast cancer, we screened paraffin-embedded breast tumor tissues by immunohistochemistry (Fig. 3). There was little or no expression in normal breast tissues (n = 15). In contrast, both ORF1p and ORF2p were differentially expressed in the breast tumors, and expressions were higher and more intense staining in DCIS than in invasive cancers. Table 1 shows the overall presence or the absence of the ORF1p and ORF2p expression regardless of location.Fig. 3

Bottom Line: The majority of invasive cancers were found to express both ORF1p and ORF2p in the cytoplasm, while nuclear expression was also seen in a subclass of those invasive cancers in the range of 28-31 %.Tumors with high nuclear expression of ORF1p and ORF2p were more significantly associated with lymph node metastasis (p = 0.001) and the worst patient survival (p < 0.0001) than those with cytoplasmic expression.Our observation shows altered expression patterns of ORF1p and ORF2p within invasive cancers, which are related to differences in overall patient survival.

View Article: PubMed Central - PubMed

Affiliation: John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia.

ABSTRACT
Long interspersed nuclear element 1 (L1) belongs to a family of retrotransposons. Expression of the normally repressed L1 retrotransposons has been shown to induce genome instability by creating DNA double-stranded breaks and chromosomal rearrangements through the process of retrotransposition. At present, little is known about the expression of L1-encoded ORF1p and ORF2p which are indispensable for its retrotransposition activity. Given its potentially harmful effects on the genome, we investigated the implications of both ORF1p and ORF2p expression and their subcellular localization in a range of breast cancer cell lines and breast tumor tissues including 15 normal breast tissues, 25 fibroadenomas, 25 ductal carcinomas in situ (DCIS), and 95 invasive cancers. Clinicopathologic parameters and survival outcomes were investigated in association with the cytoplasmic and nuclear expression of ORF1p and ORF2p using univariate and multivariate analysis. High cytoplasmic expression of ORF1p and ORF2p was seen in DCIS tumors, but they were not related with survival outcome. The majority of invasive cancers were found to express both ORF1p and ORF2p in the cytoplasm, while nuclear expression was also seen in a subclass of those invasive cancers in the range of 28-31 %. Tumors with high nuclear expression of ORF1p and ORF2p were more significantly associated with lymph node metastasis (p = 0.001) and the worst patient survival (p < 0.0001) than those with cytoplasmic expression. This is the first study examining the effects of both ORF1p and ORF2p expression in breast cancer tissues. Our observation shows altered expression patterns of ORF1p and ORF2p within invasive cancers, which are related to differences in overall patient survival. The differing patterns of both cytoplasmic and nuclear ORF1p and ORF2p expression indicate that further studies of the biology and function of L1 retrotransposons are required in breast cancer.

Show MeSH
Related in: MedlinePlus