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The Status of STAT3 and STAT5 in Human Breast Atypical Ductal Hyperplasia.

Shi A, Dong J, Hilsenbeck S, Bi L, Zhang H, Li Y - PLoS ONE (2015)

Bottom Line: Formalin-fixed, paraffin-embedded archival tissues from 59 cases of atypical ductal hyperplasia (ADH) and 31 cases of normal human breast tissue as well as 21 cases of usual ductal hyperplasias (UDH) were obtained from the First Hospital of Jilin University, China, and stained for pSTAT3 and pSTAT5 by immunohistochemistry.In addition, both pSTAT3 and pSTAT5 were produced in similar percentages of cells in ADHs from cancer-free patients vs.ADHs that were adjacent to an invasive cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin, China; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas, United States of America.

ABSTRACT
Signal Transducer and Activation of Transcription factors (STAT3 and STAT5) play important roles in breast epithelial cell differentiation, proliferation, and apoptosis. They have been investigated extensively in established breast cancer, but their activation status in precancerous lesions has not been reported. Formalin-fixed, paraffin-embedded archival tissues from 59 cases of atypical ductal hyperplasia (ADH) and 31 cases of normal human breast tissue as well as 21 cases of usual ductal hyperplasias (UDH) were obtained from the First Hospital of Jilin University, China, and stained for pSTAT3 and pSTAT5 by immunohistochemistry. The median percentage of pSTAT5+ cells in ADH was 12%, not significantly deviant from that in normal breast. The median percentage of pSTAT3+ cells in ADH was 30%, significantly higher than that of normal breast. pSTAT3 and pSTAT5 were exclusive of each other--they were detected in different ADHs or in different cells within the same ADHs. In addition, both pSTAT3 and pSTAT5 were produced in similar percentages of cells in ADHs from cancer-free patients vs. ADHs that were adjacent to an invasive cancer. Our finding of a complementary expression pattern of pSTAT3 and pSTAT5 in ADH suggests that these two transcription factors may have feedback inhibitory effects on each other during early stages of breast cancer evolution, and that disruption of this inverse relationship may be important in the progression from early lesions to cancer, which exhibits positive association between pSTAT3 and pSTAT5.

No MeSH data available.


Related in: MedlinePlus

Complementary expression patterns of pSTAT5 and pSTAT3 in human ADH.A. Representative IHC staining for pSTAT5 (top panel) and pSTAT3 (bottom panel) in consecutive ADH lesions. B-C. Inverse correlation between percentage of pSTAT5+ and pSTAT3+ cells in ADH (B) or normal TDLU (C). Each dot represents an individual ADH lesion (B) or TDLU (C).
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pone.0132214.g002: Complementary expression patterns of pSTAT5 and pSTAT3 in human ADH.A. Representative IHC staining for pSTAT5 (top panel) and pSTAT3 (bottom panel) in consecutive ADH lesions. B-C. Inverse correlation between percentage of pSTAT5+ and pSTAT3+ cells in ADH (B) or normal TDLU (C). Each dot represents an individual ADH lesion (B) or TDLU (C).

Mentions: In normal breast epithelia, STAT5 and STAT3 are activated by different mechanisms and have different functions—STAT5 is activated during late pregnancy and lactation to promote alveologenesis and to maintain cell viability, while concurrent STAT5 deactivation and STAT3 activation at the onset of involution leads to alveolar cell apoptosis [14]. However, in invasive breast cancer, pSTAT3 has been reported to stimulate cell proliferation and to prevent apoptosis and is positively correlated with pSTAT5 [30]. In this relatively small set of normal breast samples, we did not detect a significant inverse relationship between pSTAT5-positive cells and pSTAT3-positive cells (p = 0.16, Rsp = -0.26, Fig 2C). However, among the 59 ADH cases, cases with higher pSTAT5-postive cells usually harbored fewer pSTAT3-positive cells, while cases with higher pSTAT3-positive cells often contained fewer pSTAT5-positive cells (p = 0.0047, Rsp = -0.36, Fig 2A and 2B). Careful examination of the spatial location of pSTAT5+ or pSTAT3+ cells within individual ADH cases revealed a complementary expression pattern as well—pSTAT5 and pSTAT3 were usually detected in different areas within a given precancerous lesion (Fig 2A, ADH#3). Taken together, these observations suggest that the coordinated control of pSTAT5 and pSTAT3 in normal breast epithelia is preserved in ADH and that pSTAT5 and pSTAT3 may have opposing effects on each other not only in normal breast epithelia but also in premalignant breast cells.


The Status of STAT3 and STAT5 in Human Breast Atypical Ductal Hyperplasia.

Shi A, Dong J, Hilsenbeck S, Bi L, Zhang H, Li Y - PLoS ONE (2015)

Complementary expression patterns of pSTAT5 and pSTAT3 in human ADH.A. Representative IHC staining for pSTAT5 (top panel) and pSTAT3 (bottom panel) in consecutive ADH lesions. B-C. Inverse correlation between percentage of pSTAT5+ and pSTAT3+ cells in ADH (B) or normal TDLU (C). Each dot represents an individual ADH lesion (B) or TDLU (C).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4492667&req=5

pone.0132214.g002: Complementary expression patterns of pSTAT5 and pSTAT3 in human ADH.A. Representative IHC staining for pSTAT5 (top panel) and pSTAT3 (bottom panel) in consecutive ADH lesions. B-C. Inverse correlation between percentage of pSTAT5+ and pSTAT3+ cells in ADH (B) or normal TDLU (C). Each dot represents an individual ADH lesion (B) or TDLU (C).
Mentions: In normal breast epithelia, STAT5 and STAT3 are activated by different mechanisms and have different functions—STAT5 is activated during late pregnancy and lactation to promote alveologenesis and to maintain cell viability, while concurrent STAT5 deactivation and STAT3 activation at the onset of involution leads to alveolar cell apoptosis [14]. However, in invasive breast cancer, pSTAT3 has been reported to stimulate cell proliferation and to prevent apoptosis and is positively correlated with pSTAT5 [30]. In this relatively small set of normal breast samples, we did not detect a significant inverse relationship between pSTAT5-positive cells and pSTAT3-positive cells (p = 0.16, Rsp = -0.26, Fig 2C). However, among the 59 ADH cases, cases with higher pSTAT5-postive cells usually harbored fewer pSTAT3-positive cells, while cases with higher pSTAT3-positive cells often contained fewer pSTAT5-positive cells (p = 0.0047, Rsp = -0.36, Fig 2A and 2B). Careful examination of the spatial location of pSTAT5+ or pSTAT3+ cells within individual ADH cases revealed a complementary expression pattern as well—pSTAT5 and pSTAT3 were usually detected in different areas within a given precancerous lesion (Fig 2A, ADH#3). Taken together, these observations suggest that the coordinated control of pSTAT5 and pSTAT3 in normal breast epithelia is preserved in ADH and that pSTAT5 and pSTAT3 may have opposing effects on each other not only in normal breast epithelia but also in premalignant breast cells.

Bottom Line: Formalin-fixed, paraffin-embedded archival tissues from 59 cases of atypical ductal hyperplasia (ADH) and 31 cases of normal human breast tissue as well as 21 cases of usual ductal hyperplasias (UDH) were obtained from the First Hospital of Jilin University, China, and stained for pSTAT3 and pSTAT5 by immunohistochemistry.In addition, both pSTAT3 and pSTAT5 were produced in similar percentages of cells in ADHs from cancer-free patients vs.ADHs that were adjacent to an invasive cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin, China; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas, United States of America.

ABSTRACT
Signal Transducer and Activation of Transcription factors (STAT3 and STAT5) play important roles in breast epithelial cell differentiation, proliferation, and apoptosis. They have been investigated extensively in established breast cancer, but their activation status in precancerous lesions has not been reported. Formalin-fixed, paraffin-embedded archival tissues from 59 cases of atypical ductal hyperplasia (ADH) and 31 cases of normal human breast tissue as well as 21 cases of usual ductal hyperplasias (UDH) were obtained from the First Hospital of Jilin University, China, and stained for pSTAT3 and pSTAT5 by immunohistochemistry. The median percentage of pSTAT5+ cells in ADH was 12%, not significantly deviant from that in normal breast. The median percentage of pSTAT3+ cells in ADH was 30%, significantly higher than that of normal breast. pSTAT3 and pSTAT5 were exclusive of each other--they were detected in different ADHs or in different cells within the same ADHs. In addition, both pSTAT3 and pSTAT5 were produced in similar percentages of cells in ADHs from cancer-free patients vs. ADHs that were adjacent to an invasive cancer. Our finding of a complementary expression pattern of pSTAT3 and pSTAT5 in ADH suggests that these two transcription factors may have feedback inhibitory effects on each other during early stages of breast cancer evolution, and that disruption of this inverse relationship may be important in the progression from early lesions to cancer, which exhibits positive association between pSTAT3 and pSTAT5.

No MeSH data available.


Related in: MedlinePlus