MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma Subtypes
Mismatch repair genes <i>mutS homologs 6/2</i> (<i>MSH6/2</i>) expressions are involved in tumor growth and <i>programmed cell death 1 ligand 1</i> (<i>PD-L1</i>) expression in tumor immunity, but the direct association with pituitary adenomas (PAs) is...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/8/2831 |
| _version_ | 1797570265478070272 |
|---|---|
| author | Shinsuke Uraki Hiroyuki Ariyasu Asako Doi Ken Takeshima Shuhei Morita Hidefumi Inaba Hiroto Furuta Noriaki Fukuhara Naoko Inoshita Hiroshi Nishioka Naoyuki Nakao Shozo Yamada Takashi Akamizu |
| author_facet | Shinsuke Uraki Hiroyuki Ariyasu Asako Doi Ken Takeshima Shuhei Morita Hidefumi Inaba Hiroto Furuta Noriaki Fukuhara Naoko Inoshita Hiroshi Nishioka Naoyuki Nakao Shozo Yamada Takashi Akamizu |
| author_sort | Shinsuke Uraki |
| collection | DOAJ |
| description | Mismatch repair genes <i>mutS homologs 6/2</i> (<i>MSH6/2</i>) expressions are involved in tumor growth and <i>programmed cell death 1 ligand 1</i> (<i>PD-L1</i>) expression in tumor immunity, but the direct association with pituitary adenomas (PAs) is not well understood. We aimed to clarify the effects of MSH6/2 and PD-L1 expression on tumor proliferation and invasiveness in nonfunctioning (NF) PAs. We performed immunohistochemistry to classify the NFPAs into gonadotroph adenoma (GAs), silent corticotroph adenomas (SCAs), null cell adenoma (NCAs), and pituitary transcription factor 1 (PIT1) lineage PAs. We evaluated <i>MSH6/2</i> and <i>PD-L1</i> mRNA expressions in NFPAs by real-time PCR (<i>n</i> = 73), and statistically analyzed the expressions and clinicopathological factors. We also investigated the effect of MSH6 knockout on PD-L1 expression in AtT-20ins and GH3. MSH6/2 expressions were significantly lower in invasive NFPAs than in non-invasive NFPAs, and lower in SCAs and NCAs than in GAs. <i>MSH6/2</i> expressions were positively associated with <i>PD-L1</i> expression. <i>PD-L1</i> expression was significantly lower in invasive NFPAs than in non-invasive NFPAs, and lower in SCAs and NCAs than in GAs. Although <i>MSH6/2</i> expressions also tended to be lower in PIT1 lineage PAs than in GAs, PIT1 lineage PAs expressed <i>PD-L1</i> equivalently to GA, which was unlike SCAs and NCAs. MSH6 knockout in AtT-20ins and GH3 significantly decreased <i>PD-L1</i> expression (75% and 34% reduction, respectively) with cell proliferation promotion. In conclusion, differences in <i>MSH6/2</i> and <i>PD-L1</i> expressions of SCAs, NCAs, and PIT1-lineage PAs from those of GAs appear to contribute to their clinically aggressive characteristics, such as more proliferation and invasiveness. |
| first_indexed | 2024-03-10T20:23:27Z |
| format | Article |
| id | doaj.art-a44a76b07abe4b88bff14d46ff350b70 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:23:27Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a44a76b07abe4b88bff14d46ff350b702023-11-19T22:02:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01218283110.3390/ijms21082831MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma SubtypesShinsuke Uraki0Hiroyuki Ariyasu1Asako Doi2Ken Takeshima3Shuhei Morita4Hidefumi Inaba5Hiroto Furuta6Noriaki Fukuhara7Naoko Inoshita8Hiroshi Nishioka9Naoyuki Nakao10Shozo Yamada11Takashi Akamizu12First Department of Internal Medicine, Wakayama Medical University, Wakayama 641-8509, JapanFirst Department of Internal Medicine, Wakayama Medical University, Wakayama 641-8509, JapanFirst Department of Internal Medicine, Wakayama Medical University, Wakayama 641-8509, JapanFirst Department of Internal Medicine, Wakayama Medical University, Wakayama 641-8509, JapanFirst Department of Internal Medicine, Wakayama Medical University, Wakayama 641-8509, JapanFirst Department of Internal Medicine, Wakayama Medical University, Wakayama 641-8509, JapanFirst Department of Internal Medicine, Wakayama Medical University, Wakayama 641-8509, JapanDepartment of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo 105-8470, JapanDepartment of Pathology, Tokyo Metropolitan Geriatric Medical Center, Tokyo 173-0015, JapanDepartment of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo 105-8470, JapanDepartment of Neurological Surgery, Wakayama Medical University, Wakayama 641-8509, JapanHypothalamic and Pituitary Center, Moriyama Neurological Center Hospital, Tokyo 134-0088, JapanFirst Department of Internal Medicine, Wakayama Medical University, Wakayama 641-8509, JapanMismatch repair genes <i>mutS homologs 6/2</i> (<i>MSH6/2</i>) expressions are involved in tumor growth and <i>programmed cell death 1 ligand 1</i> (<i>PD-L1</i>) expression in tumor immunity, but the direct association with pituitary adenomas (PAs) is not well understood. We aimed to clarify the effects of MSH6/2 and PD-L1 expression on tumor proliferation and invasiveness in nonfunctioning (NF) PAs. We performed immunohistochemistry to classify the NFPAs into gonadotroph adenoma (GAs), silent corticotroph adenomas (SCAs), null cell adenoma (NCAs), and pituitary transcription factor 1 (PIT1) lineage PAs. We evaluated <i>MSH6/2</i> and <i>PD-L1</i> mRNA expressions in NFPAs by real-time PCR (<i>n</i> = 73), and statistically analyzed the expressions and clinicopathological factors. We also investigated the effect of MSH6 knockout on PD-L1 expression in AtT-20ins and GH3. MSH6/2 expressions were significantly lower in invasive NFPAs than in non-invasive NFPAs, and lower in SCAs and NCAs than in GAs. <i>MSH6/2</i> expressions were positively associated with <i>PD-L1</i> expression. <i>PD-L1</i> expression was significantly lower in invasive NFPAs than in non-invasive NFPAs, and lower in SCAs and NCAs than in GAs. Although <i>MSH6/2</i> expressions also tended to be lower in PIT1 lineage PAs than in GAs, PIT1 lineage PAs expressed <i>PD-L1</i> equivalently to GA, which was unlike SCAs and NCAs. MSH6 knockout in AtT-20ins and GH3 significantly decreased <i>PD-L1</i> expression (75% and 34% reduction, respectively) with cell proliferation promotion. In conclusion, differences in <i>MSH6/2</i> and <i>PD-L1</i> expressions of SCAs, NCAs, and PIT1-lineage PAs from those of GAs appear to contribute to their clinically aggressive characteristics, such as more proliferation and invasiveness.https://www.mdpi.com/1422-0067/21/8/2831pituitary adenomamismatch repair geneMSH6MSH2tumor immunityPD-L1 |
| spellingShingle | Shinsuke Uraki Hiroyuki Ariyasu Asako Doi Ken Takeshima Shuhei Morita Hidefumi Inaba Hiroto Furuta Noriaki Fukuhara Naoko Inoshita Hiroshi Nishioka Naoyuki Nakao Shozo Yamada Takashi Akamizu MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma Subtypes International Journal of Molecular Sciences pituitary adenoma mismatch repair gene MSH6 MSH2 tumor immunity PD-L1 |
| title | MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma Subtypes |
| title_full | MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma Subtypes |
| title_fullStr | MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma Subtypes |
| title_full_unstemmed | MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma Subtypes |
| title_short | MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma Subtypes |
| title_sort | msh6 2 and pd l1 expressions are associated with tumor growth and invasiveness in silent pituitary adenoma subtypes |
| topic | pituitary adenoma mismatch repair gene MSH6 MSH2 tumor immunity PD-L1 |
| url | https://www.mdpi.com/1422-0067/21/8/2831 |
| work_keys_str_mv | AT shinsukeuraki msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes AT hiroyukiariyasu msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes AT asakodoi msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes AT kentakeshima msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes AT shuheimorita msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes AT hidefumiinaba msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes AT hirotofuruta msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes AT noriakifukuhara msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes AT naokoinoshita msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes AT hiroshinishioka msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes AT naoyukinakao msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes AT shozoyamada msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes AT takashiakamizu msh62andpdl1expressionsareassociatedwithtumorgrowthandinvasivenessinsilentpituitaryadenomasubtypes |